Solid support dirhodium catalyst compositions and methods for making and using same

ABSTRACT

Disclosed are dirhodium catalyst compositions. One such dirhodium catalyst composition includes a dirhodium catalyst and a solid support. The dirhodium catalyst includes a Rh—Rh moiety and four bridging ligand moieties. The dirhodium catalyst and the solid support are bound together, but they are not covalently bound together via one or more of the bridging ligand moieties. Another such dirhodium catalyst composition includes a dirhodium tetracarboxylate catalyst and a solid support, and the dirhodium tetracarboxylate catalyst and the solid support are bound together. Yet another such dirhodium catalyst composition includes a dirhodium catalyst and a solid support, where the dirhodium catalyst includes a Rh—Rh moiety and where the dirhodium catalyst and the solid support are bound together via at least one of the rhodiums&#39; axial positions. The compositions can be used in a number of reactions, including insertion reactions (e.g., C—H insertions, Si—H insertions, O—H insertions, and N—H insertions), cyclopropanation reactions, annulations (e.g., [3+2] annulations and [3+4] annulations), and ω,ω-diarylalkanoate synthesis. Methods for making the dirhodium catalyst compositions are also disclosed.

[0001] This application claims the benefit of U.S. Provisional PatentApplication Serial No. 60/315,147, filed Aug. 27, 2001, which is herebyincorporated by reference.

[0002] The present invention was made with the support of the NationalScience Foundation, Contract No. CHE 0092490, and the NationalInstitutes of Health, Contract No. CA85641 and Contract No. GM57425. TheFederal Government may have certain rights in this invention.

FIELD OF THE INVENTION

[0003] The present invention relates, generally, to metal catalystcompositions and to methods for using such compositions and, moreparticularly, to compositions containing dirhodium catalyst on a solidsupport and to methods for using such compositions.

BACKGROUND OF THE INVENTION

[0004] Dirhodium catalysts have been employed as catalysts in a varietyof chemical reactions. One of the major drawbacks of using dirhodiumcatalysts is the expense of rhodium metal. Typically, to overcome thecosts associated with catalysts containing expensive metals, twoapproaches can be used: (i) increasing the efficiency (e.g., turnovernumber and/or turnover rate) of the catalyst and/or (ii) recovering thespent catalyst from the reaction mixture so that the expensive metal canbe separated and recycled. Neither approach has had much success withchiral dirhodium catalysts.

[0005] The present invention is directed to dirhodium catalystcompositions in which a dirhodium catalyst is attached to a solidsupport, for example, to facilitate recovery of spent catalyst from areaction mixture.

SUMMARY OF THE INVENTION

[0006] The present invention relates to a dirhodium catalyst compositionwhich includes a dirhodium catalyst and a solid support. The dirhodiumcatalyst includes a Rh—Rh moiety and four bridging ligand moieties. Thedirhodium catalyst and the solid support are bound together, but theyare not covalently bound together via one or more of the bridging ligandmoieties.

[0007] The present invention also relates to a dirhodium catalystcomposition which includes a dirhodium tetracarboxylate catalyst and asolid support, and the dirhodium tetracarboxylate catalyst and the solidsupport are bound together.

[0008] The present invention also relates to a dirhodium catalystcomposition which includes a dirhodium catalyst and a solid support. Thedirhodium catalyst includes a Rh—Rh moiety, and the dirhodium catalystand the solid support are bound together via at least one of therhodiums' axial positions.

DETAILED DESCRIPTION OF THE INVENTION

[0009] The present invention, in one aspect thereof, relates to adirhodium catalyst composition which includes a dirhodium catalyst and asolid support. The dirhodium catalyst includes a Rh—Rh moiety and fourbridging ligand moieties. The dirhodium catalyst and the solid supportare bound together, but they are not covalently bound together via oneor more of the bridging ligand moieties.

[0010] The present invention, in another aspect thereof, relates to adirhodium catalyst composition which includes a dirhodiumtetracarboxylate catalyst and a solid support, and the dirhodiumtetracarboxylate catalyst and the solid support are bound together.

[0011] The present invention, in yet another aspect thereof, relates toa dirhodium catalyst composition which includes a dirhodium catalyst anda solid support. The dirhodium catalyst includes a Rh—Rh moiety, and thedirhodium catalyst and the solid support are bound together via at leastone of the rhodiums' axial positions.

[0012] As used herein, “alkyl” is meant to include linear alkyls,branched alkyls, and cycloalkyls, each of which can be substituted orunsubstituted. “Alkyl” is also meant to include lower linear alkyls(e.g., C1-C6 linear alkyls), such as methyl, ethyl, n-propyl, n-butyl,n-pentyl, and n-hexyl; lower branched alkyls (e.g., C3-C8 branchedalkyls), such as isopropyl, t-butyl, 1-methylpropyl, 2-methylpropyl,1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,2-dimethylpropyl,1,1-dimethylpropyl, 2,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl,3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl,1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl,3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 2-methyl-2-ethylpropyl,2-methyl-l-ethylpropyl, and the like; and lower cycloalkyls (e.g., C3-C8cycloalkyls), such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,and the like. “Alkyl”, as use herein, is meant to include unsubstitutedalkyls, such as those set forth above, in which no atoms other thancarbon and hydrogen are present. “Alkyl”, as use herein, is also meantto include substituted alkyls. Suitable substituents include aryl groups(which may themselves be substituted), heterocyclic rings (saturated orunsaturated and optionally substituted), alkoxy groups (which is meantto include aryloxy groups (e.g., phenoxy groups)), amine groups (e.g.,disubstituted with aryl or alkyl groups), carboxylic acid derivatives(e.g., carboxylic acid esters, amides, etc.), halogen atoms (e.g., Cl,Br, and I), and the like. Further, alkyl groups bearing one or morealkenyl or alkynyl substituents (e.g., a methyl group itself substitutedwith a prop-1-en-1-yl group to produce a but-2-en-1-yl substituent) ismeant to be included in the meaning of “alkyl”.

[0013] As used herein, “alkoxy” is meant to include groups having theformula —O—R, where R is an alkyl or aryl group. They include methoxy,ethoxy, propoxy, phenoxy, 4-methylphenoxy, and the like.

[0014] As used herein, “aryl” is meant to include aromatic rings, forexample, aromatic rings having from 4 to 12 members, such as phenylrings. These aromatic rings can optionally contain one or moreheteroatoms (e.g., one or more of N, O, and S), and, thus, “aryl”, asused herein, is meant to include heteroaryl moieties, such as pyridylrings and furanyl rings. The aromatic rings can be optionallysubstituted. “Aryl” is also meant to include aromatic rings to which arefused one or more other aryl rings or non-aryl rings. For example,naphthyl groups, indole groups, and 5,6,7,8-tetrahydro-2-naphthyl groups(each of which can be optionally substituted) are aryl groups for thepurposes of the present application. As indicated above, the aryl ringscan be optionally substituted. Suitable substituents include alkylgroups (which can optionally be substituted), other aryl groups (whichmay themselves be substituted), heterocyclic rings (saturated orunsaturated), alkoxy groups (which is meant to include aryloxy groups(e.g., phenoxy groups)), amine groups (e.g., disubstituted with aryl oralkyl groups), carboxylic acid groups, carboxylic acid derivatives(e.g., carboxylic acid esters, amides, etc.), halogen atoms (e.g., Cl,Br, and I), and the like

[0015] As used herein, “ring” refers to a homocyclic or heterocyclicring which can be saturated or unsaturated. The ring can beunsubstituted, or it can be substituted with one or more substituents.The substituents can be saturated or unsaturated, aromatic ornonaromatic, and examples of suitable substituents include those recitedabove in the discussion relating to substituents on alkyl and arylgroups. Furthermore, two or more ring substituents can combine to formanother ring, so that “ring”, as used herein, is meant to include fusedring systems. In the case where the ring is saturated (i.e., in the casewhere each of the atoms making up the ring are joined by single bonds toother members of the ring), the ring may optionally include unsaturated(aromatic or nonaromatic) or saturated substituents.

[0016] As used herein, “solid support” is meant to include any materialwhich can be bonded to the dirhodium catalyst and which can be separatedfrom a liquid or solution, such as by filtration, centrifugation,decantation, and/or combinations thereof.

[0017] The solid support can be uniform through its thickness or it canbe coated on a substrate (e.g., an inert substrate), such as on astainless steel, glass, or other types of rod; stainless steel, glass,or other types of beads; the interior walls of reaction vessels, or aportion thereof; and the like.

[0018] A variety of solid supports can be used in the practice of thepresent invention.

[0019] For example, the solid support can be one which includes anitrogen-containing heterocyclic pendant group. In this regard, suitablenitrogen-containing heterocyclic pendant groups include, for example,pyridyl groups, quinolinyl groups, isoquinolinyl groups, imidazolylgroups, benzimidazolyl groups, and the like. Illustratively, the pendantgroup can be bound to a polymeric solid support by conventional polymerchemistry to produce the desired solid support. How the pendant group isbonded into the solid support is not particularly critical to thepractice of the present invention. Covalent bonding of the pendant groupinto a polymeric solid support is illustrative.

[0020] In one illustrative embodiment of the present invention, thesolid support is a macroporous solid support; or it is a cross-linkedpolystyrene resin; or it is both.

[0021] As used herein, “macroporous solid support” is meant to includesolid supports which have a porosity (e.g., pore size) substantially thesame as the porosity of Argopore-Wang Resin. For purposes of the presentinvention, Resin A is to be deemed as having substantially the same asthe porosity as Resin B if the ratio of the the average pore size ofResin A to the average pore size of Resin B is between about 0.5 andabout 1.5, such as between about 0.6 and about 1.4, between about 0.7and about 1.3, between about 0.8 and about 1.2, between about 0.9 andabout 1.1, and/or between about 0.95 and about 1.05.

[0022] Suitable cross-linked polystyrene resins (whether macroporous ornot) include those which are more highly cross-linked than a 1%cross-linked polystyrene resin. The degree of cross-linking can beascertained by any conventional method known to those skilled in theart.

[0023] Additionally or alternatively, the solid support can be across-linked polystyrene resin (i.e., a cross-linked resin having apolystyrene backbone) which includes pendant groups having the formula:

[0024] wherein W represents H, halogen, a hydroxy group, a thiol group,an alkoxy group, an alkylthio group, an aryl thio group, or combinationsthereof. Illustratively, the cross-linked polystyrene resin can be onebearing pendant groups having the above formula in which W represents a—OW′ group and in which W′ is an aryl group, such as in the case whereW′ represents a substituted or unsubstituted phenyl group or asubstituted or unsubstituted pyridyl group (e.g., a 4-pyridyl group). Asfurther illustration of the variety of groups that can be used for W′,W′ can represent any nitrogen-containing heterocycle, for example, apyridyl group (as mentioned above), a quinolinyl group, an isoquinolinylgroup, an imidazolyl group, or a benzimidazolyl group.

[0025] Still other suitable solid supports are those having a polymerbackbone (e.g., a cross-linked polystyrene resin) which includes pendantgroups having the formula:

[0026] wherein W has the meaning set forth in the preceding paragraph.

[0027] A variety of other considerations can be taken into account whenchoosing a solid support. These include, for example, the propensity ofthe solid support to adhere to reaction vessels (glass, stainless steel,etc.); the effect of the length of a pendant group on possible stericinteractions between the dirhodium catalyst and the polymer backbone;the compatibility of the solid support with various solvents to which itmay be exposed; the solid support's swelling characteristics; and thelike.

[0028] As used herein, “dirhodium catalyst” is meant to include anymaterial which is, can be, or has been used as a catalyst and whichcontains two rhodium atoms and/or ions that are bonded with one another.The nature of the bond between the two rhodium atoms is not limitative:it can be covalent, ionic, van der Walls, pi-pi, sigma-pi, etc., orcombinations of these. Of course, the dirhodium catalyst can includeother atoms or ions or groups of atoms (e.g., ligands). Illustratively,each rhodium in the dirhodium catalyst can have a formal charge of +2,and the charge on the overall complex can be neutral.

[0029] Examples of “dirhodium catalysts” include catalysts having theformula L₄Rh—RhL₄ where each of the L's is the same or different andrepresents a coordinating atom from one or more ligands.

[0030] In certain aspects of the present invention, the dirhodiumcatalyst includes a Rh—Rh moiety and four bridging ligand moieties. Asused herein, a “bridging ligand moiety” is meant to refer to a moietywhich bridges between the two rhodium atoms. Suitable “bridging ligandmoieties” include, for example, carboxylate moieties and amide moieties.For example, the dirhodium catalyst can include a Rh—Rh moiety and fourbridging ligand moieties where each of the four bridging ligand moietiesare independently selected from carboxylate moieties (each of whichprovides two coordinating oxygen atoms bonded to a single carbon atom)and amide moieties (each of which provides one coordinating oxygen atomand one coordinating nitrogen atom bonded to a single carbon atom). Inthis context, the dirhodium catalyst can be, for example, a dirhodiumtetracarboxylate catalyst (i.e., a catalyst having the formula L₄Rh—RhL₄where each of the L's represents a carboxylate oxygen from one of fourcarboxylate groups); a dirhodium tetracarboxamidate catalyst (i.e., acatalyst having the formula L₄Rh—RhL₄ where four of the L's represent acarbonyl oxygen from one of four amide groups and where the remainingfour L's represent a nitrogen from one of four amide groups); adirhodium tricarboxylate monocarboxamidate catalyst (i.e., a catalysthaving the formula L₄Rh—RhL₄ where six of the L's each represent acarboxylate oxygen from one of three carboxylate groups, where one ofthe L's represents a carbonyl oxygen the amide group, and where theremaining L represents a nitrogen from the amide group); a dirhodiumdicarboxylate dicarboxamidate catalyst (i.e., a catalyst having theformula L₄Rh—RhL₄ where four of the L's each represent a carboxylateoxygen from one of two carboxylate groups, where two of the L's eachrepresent a carbonyl oxygen one of two amide groups, and where theremaining two L's each represent a nitrogen from one of two amidegroups); or a dirhodium monocarboxylate tricarboxamidate catalyst (i.e.,a catalyst having the formula L₄Rh—RhL₄ where two of the L's eachrepresent a carboxylate oxygen from the carboxylate group, where threeof the L's each represent a carbonyl oxygen from one of three amidegroups, and where the remaining three L's each represent a nitrogen fromone of three amide groups).

[0031] Examples of dirhodium tetracarboxylate catalysts includedirhodium acetate dimer, dirhodium propionate dimer, dirhodium butyratedimer, dirhodium pentanoate dimer, dirhodium hexanoate dimer, dirhodiumheptanoate dimer, dirhodium octanoate dimer, fluorinated analogs thereof(e.g. dirhodium heptafluorobutyrate dimer), and combinations thereof.

[0032] Other illustrative examples of dirhodium tetracarboxylatecatalysts include those having the formula (“Formula I”):

[0033] In Formula I, each of M¹ and M² is Rh. Z⁴ represents the atomsnecessary to complete a 3-12 membered heterocyclic ring, such as analkylene moiety (e.g., a —CH₂CH₂CH₂-moiety). Q³ is an electronwithdrawing group, such as a group having the formulae —C(O)R⁹, —SO₂R⁹,or —P(O)R⁹R^(9′), where each of R⁹ and R^(9′) is independently selectedfrom an alkyl group, an aryl group, and an alkoxy group.

[0034] As used herein, “electron withdrawing group” refers to thosegroups which are able to withdraw electron density from adjacentpositions in a molecule, as determined, for example, by reference to thetables in the classical works which establish the classification ofvarious substituents according to their electron withdrawing character.For example, reference may be made to the classification established bythe Hammett scale, such as the one set forth in Gordon et al., TheChemist's Companion, New York: John Wiley & Sons, pp. 145-147 (1972)(“Gordon”), which is hereby incorporated by reference. Suitableelectron-withdrawing groups include those having a para σ value higherthan or equal to about 0.2 or higher than or equal to about 0.3, withreference to the Hammett scale. Particular examples of electronwithdrawing groups are moieties having the formulae —C(O)R, —SO₂R, and—P(O)RR′, where R and R′ are independently selected from an alkyl group,an aryl group, and an alkoxy group.

[0035] As used herein, “alkylene” refers to a bivalent alkyl group,where alkyl has the meaning given above. Linear, branched, and cyclicalkylenes, as well as examples thereof, are defined in similar fashionwith reference to their corresponding alkyl group. Examples of alkylenesinclude eth-1,1-diyl (i.e., —CH(CH₃)—), eth-1,2-diyl (i.e., —CH₂CH₂—),prop-1,1-diyl (i.e., —CH(CH₂CH₃)—), prop-1,2-diyl (i.e.,—CH₂—CH(CH₃)—),prop-1,3-diyl (i.e., —CH₂CH₂CH₂—), prop-2,2-diyl (e.g. —C(CH₃)₂—),cycloprop-1,1-diyl, cycloprop-1,2-diyl, cyclopent-1,1-diyl,cyclopent-1,2-diyl, cyclopent-1,3-diyl, cyclohex-1,1-diyl,cyclohex-1,2-diyl, cyclohex-1,3-diyl , cyclohex-1,4-diyl,but-2-en-1,1-diyl, cyclohex-1,3-diyl, but-2-en-1,4-diyl,but-2-en-1,2-diyl, but-2-en-1,3-diyl, but-2-en-2,3-diyl. Also includedin the meaning of the term “alkylene” are compounds having the formula—R′—R″—, where —R′ represents a linear or branched alkyl group and R″—represents a cycloalkyl group, such as moieties having the formula:

[0036] In Formula I and in all other formulae set forth in this documentwhich contain one or more chiral centers and which do not specify thestereochemistry of a particular chiral center, such formulae are to beconstrued as encompassing all possible stereochemistries. Thus, forexample, Formula I is meant to include (i) compounds in which theunspecified chiral center is entirely in the R configuration, (ii)compounds in which the unspecified chiral center is entirely in the Sconfiguration, and (iii) racemic and other mixtures of (i) and (ii).Illustratively, dirhodium tetracarboxylate catalysts of Formula I aremeant to include substantially chirally pure catalysts having one of thefollowing formulae (“Formula II-A” and “Formula II-B”, respectively):

[0037] as well as dirhodium tetracarboxylate catalysts of Formula Ihaving D₂ symmetry. Molecules having D₂ symmetry are molecules whichhave a vertical C₂ axis and a set of two C₂ axes perpendicular to thevertical C₂ axis. D₂ symmetry is further described in, for example,Cotton et al., Advanced Inorganic Chemistry, 4th ed., New York: JohnWiley & Sons, pages 28-46 (1980), which is hereby incorporated byreference.

[0038] Specific examples of suitable catalysts having Formulae I and IIinclude: Rh₂(DOSP)₄, Rh₂(S-DOSP)₄, and Rh₂(R-DOSP)₄, which are compoundshaving Formulae I, II-A, and II-B, respectively, in which each of M¹ andM² is Rh, Z⁴ is a —CH₂CH₂CH₂— group, and Q³ represents a4-dodecylphenylsulfonyl moiety; and Rh₂(TBSP)₄, Rh₂(S-TBSP)₄, andRh₂(R-TBSP)₄, which are compounds having Formulae I, II-A, and II-B,respectively, in which each of M¹ and M² is Rh, Z⁴ is a —CH₂CH₂CH₂—group, and Q³ represents a 4-t-butylphenylsulfonyl moiety. These andother illustrative compounds having Formulae I, II-A, and II-B aredescribed in greater detail in Davies, “Rhodium-StabilizedVinylcarbenoid Intermediates in Organic Synthesis,” Current OrganicChemistry, 2:463-488 (1998), which is hereby incorporated by reference.

[0039] Other suitable dirhodium tetracarboxylate catalysts include thosewhich contain two rhodium atoms or ions that are bonded to one anotheralong an axis. This can be represented by the formula Rh—Rh, where thedash represents the Rh-to-Rh bond and the bond axis. These catalystsalso contain two carboxylate ligands. As used herein, “carboxylateligands” means ligands which contain one or more carboxylate groups. Asused herein, carboxylate groups mean groups having the formula:

[0040] which can be written with the following formula:

[0041] where the dashed line represents the delocalized electrons.Alternatively, the carboxylate group can be expressed without showingthe delocalized electrons, as in the following formula:

[0042] Each of the two carboxylate ligands includes two carboxylategroups, and these two carboxylate groups are bonded to each other via amoiety having the formula (“Formula III”):

[0043] In Formula III, Z¹⁰ and Z¹¹, together with the atoms to whichthey are bonded form a 3-12 membered ring, and Z^(10′) and Z^(11′),together with the atoms to which they are bonded form a 3-12 memberedring. Z¹⁰ and Z^(10′) can be the same, and each can contain aheteroatom, such as a nitrogen, oxygen, or sulfur. For example in oneembodiment, Z¹⁰ and Z^(10′) are the same, and each represents a singleheteroatom selected from the group consisting a sulfur atom, an oxygenatom, and an optionally substituted nitrogen atom. In anotherillustrative embodiment, at least one of Z¹⁰ and Z^(10′) has the formula—NQ—, at least one of Z¹¹ and Z^(11′) is an arylene or alkylene group,and Q is an electron withdrawing group. In yet another illustrativeembodiment, each of Z¹⁰ and Z^(10′) has the formula —NQ—, each of Z¹¹and Z^(11′) is an alkylene group, and Q is an electron withdrawinggroup. Although one of Z¹⁰ and Z¹¹ and/or one of Z^(10′) and Z^(11′) canrepresent a direct bond between the carbons to which they are attached,this need not be the case, for example as when only three, only two,only one, or none of Z¹⁰, Z¹¹, Z^(10′), and Z^(11′) represents such adirect bond. R⁷⁸, R^(78′), R⁷⁹, and R^(79′) are independently selectedfrom the group consisting of H, an alkyl group, and an aryl group, suchas in the case where each of R⁷⁸, R^(78′), R⁷⁹, and R^(79′) represents ahydrogen. Z¹² represents an alkylene or arylene group, such as asubstituted or unsubstituted 1,3-phenylene group.

[0044] As indicated in the formulae above, each of the two carboxylategroups includes a first carboxylate oxygen atom (“O¹”), a secondcarboxylate oxygen atom (“O²”), and a carbon (“C”) to which the O¹ andthe O² are bonded thereby forming two O¹—C—O² moieties. O¹ of each ofthe two carboxylate groups of each of the two carboxylate ligands isbonded to the first rhodium (Rh¹); O² of each of the two carboxylategroups of each of the two carboxylate ligands is bonded to the secondrhodium (Rh²).

[0045] Each of the two carboxylate ligands further includes at least twostereocenters. These stereocenters, for example, can be included in oneor more of Z¹⁰, Z¹¹, Z^(10′), and Z^(11′), and/or they can be located atthe carbon atoms to which Z¹⁰, Z¹¹, Z^(10′), and Z^(11′) are bonded. Thestereochemistry at these stereocenters are selected such that thecatalyst, taken as a whole, has D₂ symmetry.

[0046] Illustrative examples of such dirhodium tetracarboxylatecatalysts include those having the formula (“Formula IV”):

[0047] In Formula IV, M¹ and M² represent rhodium atoms or ions. Z² andZ³, independently, are the atoms necessary to complete a 3-12 memberedheterocyclic ring. Examples of such atoms include, for example:substituted or unsubstituted alkylene moieties, such as those having theformula —(CH₂)_(i)—, where i is an integer from 1 to 8; and moietieshaving the formula —(CH₂)_(i)—X—(CH₂)_(j)—, where i and j eachindependently represent integers from 0 to 4 and X is a heteroatom, suchas O, S, and NR⁷⁰, where R⁷⁰ is a substituted or unsubstituted alkyl,aryl, or heteroaryl group. Illustratively, Z² and Z³ can be the same, asin the case where each of Z² and Z³ has the formula —CH₂CH₂—. Z¹ is analkylene or arylene group. Illustratively, Z¹ can have the formula—(CH₂)_(i)—, where i is an integer from 1 to 8. Alternatively, Z¹ canhave the formula —(CH₂)_(i)—X—(CH₂)_(j)—, where i and j eachindependently represent integers from 0 to 4 and X is a heteroatom, suchas O, S, and NR⁷⁰, where R⁷⁰ is an alkyl or aryl group. Stillalternatively, Z¹ can be a cycloalkyl moiety, such as cyclopent-1,3-diyland cyclohex-1,3-diyl, which can be substituted or unsubstituted. Stillalternatively, Z¹ can be an arylene moiety, such as a 1,3-phenylene or1,3-naphthylene, or an heterocyclic moiety, such as a pyrid-3,5-diyl,pyrid-2,6-diyl, 2H-pyran-3,5-diyl, and tetrohydropyran-3,5-diyl moiety.Q¹ and Q² are the same or different and are electron withdrawing groups.Examples of Q¹ suitable for use in the practice of the present inventionare moieties having the formulae —C(O)R¹, —SO₂R¹, and —P(O)R¹R^(1′), andexamples of suitable Q² include moieties having the formulae —C(O)R²,—SO₂R², and —P(O)R²R^(2′). In these formulae, each of R¹, R^(1′), R²,and R^(2′) is independently selected from an alkyl group, an aryl group,and an alkoxy group. In one illustrative embodiment, Q¹ has the formula—SO₂R¹; Q² has the formula —SO₂R²; and R¹ and R² are the same ordifferent and are substituted or unsubstituted alkyl or aryl groups,such as in the case where Q¹ has the formula —SO₂R¹; Q² has the formula—SO₂R²; and each of R¹ and R² is independently selected from the groupconsisting of 4-(t-butyl)phenyl, 2,4,6-trimethylphenyl, and2,4,6-triisopropylphenyl. In the above Formula IV, L¹ and L³, takentogether, represent a —O—CR¹³—O— moiety, and L² and L⁴, taken together,represent a —O—CR¹⁴—O— moiety. In these moieties, R¹³ and R¹⁴ can be thesame or they can be different, and each is independently selected fromthe group consisting of alkyl groups and aryl groups. Alternatively, R¹³and R¹⁴ can represent alkylene or arylene groups that are directly orindirectly bonded to one another. In the latter case, the dirhodiumtetracarboxylate catalysts of Formula IV can be expressed as thefollowing formula (“Formula V”):

[0048] where R⁷² represents an alkylene or arylene group.Illustratively, R⁷² can be selected such that the dirhodiumtetracarboxylate catalysts of Formula V have the following formula(“Formula VI”):

[0049] The dirhodium tetracarboxylate catalysts of Formulae IV, V, andVI have at least four stereocenters (i.e., at least the two carbons towhich Z² is bonded and at least the two carbons to which Z³ is bondedare stereocenters). Formulae IV, V, and VI are not meant to be limitedto any particular set of configurations at the catalyst's stereocenters,and the structures given in these formulae are meant to be broadly readto include any and all possible collections of stereocenters. Forexample, catalysts of Formula VI are meant to include (i) compoundshaving the formula (“Formula VII”):

[0050] and (ii) compounds having the formula (“Formula VIII”):

[0051] Each of the catalysts having Formulae VII and VIII can be presentalone (i.e., as a pure diastereoisomer), or it can be present in amixture with one or more different diastereoisomers. Alternatively, thecatalysts having Formulae VII and VIII can be substantially free ofother diastereoisomers. In this context, “substantially free of otherdisatereoisomers” means that the molar ratio of other diastereoisomersto the catalyst is less than 40%, such as less than 30%, less than 20%,less than 10%, less than 5%, less than 2%, and/or less than 1%.

[0052] Examples of catalysts having Formula VII and VIII, respectively,are those having the formula (“Formula IX”):

[0053] and those having the formula (“Formula X”):

[0054] Still other examples of catalysts having Formula VII and VIII,respectively, are those having the formula (“Formula XI”):

[0055] and those having the formula (“Formula XII”):

[0056] In Formula XI and Formula XII, R¹ and R² can be the same ordifferent and each can be selected from, for example, alkyl groups andaryl groups.

[0057] As used in the above discussion and elsewhere herein, “arylene”is meant to include a bivalent aryl group in which both valencies arepresent on aromatic carbons. Examples of such groups include, forexample, 1,3-phenylene, 1,4-phenylene, 5-methyl-1,3-phenylene,pyrid-2,3-diyl, pyrid-2,4-diyl, pyrid-2,5-diyl, pyrid-3,5-diyl,1,3-naphthylene, 1,7-naphthylene, 1,8-naphthylene,5,6,7,8-tetrahydro-1,3-naphthylene, thiophene-2,5-diyl, andfuran-2,5-diyl. “Arylene”, as used herein, is also meant to include abivalent group having the formula —R—R′—, where R is an alkyl group andR′ is an aryl group. As the structure of —R—R′— indicates, one of thevalencies is on the R (i.e., alkyl) portion of the —R—R′— moiety and theother of the valencies resides on the R′ (i.e., aryl) portion of the—R—R′— moiety. Examples of this type of arylene moiety include moietieshaving the formulae:

[0058] and the like.

[0059] Other suitable dirhodium tetracarboxylate catalysts as well asmethods for making various dirhodium tetracarboxylate catalysts aredescribed in, for example, U.S. Pat. No. 6,410,746 to Davies;International Publication No. WO 00/64583; and Davies et al., “NovelDirhodium Tetraprolinate Catalysts Containing Bridging Prolinate LigandsFor Asymmetric Carbenoid Reactions,” Tetrahedron Letters, pages5287-5290 (1999), each of which is hereby incorporated by reference.

[0060] Other suitable dirhodium tetracarboxylate catalysts includedirhodium tetracarboxamidate catalysts, such as those having thefollowing formula (“Formula XIII”):

[0061] In Formula XIII, each of M¹ and M² is Rh. W³ represents an alkylgroup, an aryl group, an alkoxy group, or an amine group, and W⁴represents an alkyl group or an aryl group. Alternatively, W³ and W⁴,taken together with the atoms to which they are bonded, represent a 3-12membered ring, for example, as shown in the following formula (“FormulaXIV”):

[0062] In Formula XIV, Z⁴ represents the atoms necessary to complete a3-12 membered ring. The ring can be substituted or unsubstituted; and itcan include additional heteroatoms (i.e., in addition to the N to whichZ⁴ is bonded, or it can consist only of carbons (except for the N towhich Z⁴ is bonded). Illustratively, Z⁴, together with the carbon and Natoms to which it is bonded, can represents a substituted orunsubstituted C3-C8 lactam ring, a substituted or unsubstitutedoxazolidone ring, a substituted or unsubstituted pyrrolidone ring, or asubstituted or unsubstituted imidazolidone ring. Specific examples ofsuitable catalysts of Formula XIV include: dirhodium(II)tetrakis(caprolactam); dirhodium(II) tetrakis[methyl2-oxazolidone-4-carboxylate]; dirhodium(II) tetrakis[methyl2-oxazolidone-4-(S)-carboxylate]; dirhodium(II) tetrakis[methyl2-pyrrolidone-5-carboxylate]; dirhodium(II) tetrakis[methyl2-pyrrolidone-5(R)-carboxylate]; dirhodium(II) tetrakis[methyl2-pyrrolidone-5(S)-carboxylate]; dirhodium(II) tetrakis[methyl1-(3-phenylpropanoyl)-2-imidazolidone-4-carboxylate; dirhodium(II)tetrakis[methyl 1-(3-phenylpropanoyl)-2-imidazolidone-4(S)-carboxylate;and adducts (e.g., acetonitrile and/or alcohol adducts) thereof. Methodsfor producing these and other dirhodium tetracarboxamidate catalysts canbe found, for example, in U.S. Pat. No. 5,175,311 to Doyle, which ishereby incorporated by reference.

[0063] As indicated above, in the dirhodium catalyst compositions of thepresent invention, the dirhodium catalyst and the solid support arebound together. As used herein, “bind” or “bound” is meant to refer toany form of attachment, including, for example, covalent, ionic, van derWalls, pi-pi, sigma-pi, etc. or combinations of these forms ofattachment. As used herein, “bind” or “bound” is also meant to refer tomechanical forms of attachment, where, for example, binding occursprimarily via mechanical sequestration and/or encapsulation (e.g., whereone compound is trapped in a pore of another material). As used herein,“bind” or “bound” is also meant to refer to forms of attachment in whichthe product of binding is thermodynamically stable or in which theproduct of binding is thermodynamically unstable but which is stabilizedkinetically.

[0064] In certain aspects of the present invention, the dirhodiumcatalyst and the solid support are bound together, but they are notcovalently bound together via one or more of the ligand moieties. Withregard to such aspects of the present invention, the dirhodium catalystand the solid support are to be deemed to be “not covalently boundtogether via one or more of the ligand moieties” if and only if none ofthe ligand moieties are connected to the solid support (i) via acovalent bond or (ii) via a series of bonds, all of which are covalent.In this context, a bond is to be deemed to be covalent if and only if itinvolves the sharing of electrons, such as in the case where the bond isa carbon/carbon bond, a carbon/oxygen bond, a carbon/nitrogen bond, andthe like.

[0065] In other certain aspects of the present invention, the dirhodiumcatalyst and the solid support are bound together via at least one ofthe rhodiums' axial positions. With regard to such aspects of thepresent invention, the dirhodium catalyst and the solid support are tobe deemed to be “bound together via at least one of the rhodiums' axialpositions” if and only if there is a bond between an axial position ofone of the rhodium atoms and one of the atoms of the solid support. Asis implicit in all of the above discussion, atoms of pendant groupswhich are bound directly or indirectly to the solid supportinfrastructure (e.g., a polymer backbone) are, for the purposes of thepresent invention, considered to be “atoms of the solid support”.Furthermore, as used herein, a rhodium's axial position is meant torefer to the position which is substantially in line with the Rh—Rh bond(as distinguished, for example, from the rhodium's equatorialpositions).

[0066] The dirhodium catalyst compositions described above can beproduced by a variety of methods.

[0067] For example, dirhodium catalyst compositions of the presentinvention can be produced by providing a dirhodium catalyst andcontacting the dirhodium catalyst with a solid support under conditionseffective to bind the dirhodium catalyst and the solid support togetherand to produce the dirhodium catalyst composition.

[0068] The dirhodium catalyst which is employed in this method can bepurchased commercially, or it can be prepared using any suitable method,such as those described in U.S. Pat. No. 6,410,746 to Davies; U.S. Pat.No. 5,175,311 to Doyle; International Publication No. WO 00/64583; andDavies et al., “Novel Dirhodium Tetraprolinate Catalysts ContainingBridging Prolinate Ligands For Asymmetric Carbenoid Reactions,”Tetrahedron Letters, pages 5287-5290 (1999), each of which is herebyincorporated by reference.

[0069] Suitable solid supports can be obtained commercially, or they canbe prepared by methods well known to those skilled in the art. Forexample, in cases where polymeric solid supports bearing pendant groupsare used, such solid supports can be obtained commercially, or they canbe prepared using standard techniques for adding pending groups topolymeric backbones. Illustratively, starting with a polymer whichincludes pendant hydroxyl groups, the hydroxyl groups can be convertedto bromides (e.g., using conventional triphenylphosphine/bromoformchemistry). The resulting bromide can be reacted with a suitable metalalkoxide (e.g., one having the formula D—OM″, where M represents analkali metal and D represents the pendant group to be incorporated intothe solid support), such as sodium 4-pyridinylmethoxide or anotheralkali metal 4-pyridinylmethoxide. In cases where silica based solidsupports (e.g., glass, ceramics, and the like) are employed, the silicamaterial can be functionalized with reactive groups using conventionalsilane chemistry (e.g., using functional trialkoxysilanes), which canthen be reacted with the desired pendant group. Alternatively, again incases where silica based solid supports are employed, the pendant groupcan be introduced by direct attachment to the silica material, forexample, by treating the silica material with a trialkoxysilane bearingthe desired pendant group. In cases where the solid support is based ona perfluorinated polymer (e.g., PTFE), the perfluorinated polymer can befunctionalized with reactive oxygen groups using plasma and coronadischarge treatments, ion beam and electron beam bombardment, x-ray andgamma ray treatments, treatments involving sodium metal/ammonia,treatments involving sodium naphthalene in glycol ether, treatmentsinvolving radio frequency glow discharge, and the like, for example, asdescribed in Lee et al., “Wet-process Surface Modification of DielectricPolymers: Adhesion Enhancement and Metallization,” IBM J. Res. Develop.,38(4) (July 1994); Vargo et al., “Adhesive Electroless Metallization ofFluoropolymeric Substrates,” Science, 262:1711-1712 (1993); Rye et al.,“Synchrotron Radiation Studies of Poly(tetrafluoroethylene)Photochemistry,” Langmuir, 6:142-146 (1990); Tan et al., “Investigationof Surface Chemistry of Teflon. 1. Effect of Low Energy Argon IonIrradiation on Surface Structure,” Langmuir, 9:740-748 (1993), U.S. Pat.No. 5,051,312 to Allmer, and U.S. Pat. Nos. 4,946,903, 5,266,309, and5,627,079, each to Gardella Jr. et al., which are hereby incorporated byreference. Subsequent reaction of the functionalized perfluorinatedpolymer with a suitably functionalized compound bearing the desiredpendant group can be used to complete the preparation of the solidsupport.

[0070] The aforementioned dirhodium catalysts and solid supports can beprovided neat (i.e., in the absence substantially all other materials)or either the dirhodium catalyst or the solid support or both can beprovided as a mixture with other materials, such as, for example,solvents, reactants, and the like. Where the dirhodium catalyst isprovided in solution form, it can be provided in concentrated form(e.g., at a concentration greater than about 5 times the concentrationat which they will be used in a catalytic reaction), or it can beprovided in dilute form (e.g., at a concentration less than about 5times the concentration at which they will be used in the catalyticreaction). Where solvents are employed, it is desirable that the solventused to suspend the solid support and the solvent used to dissolve orsuspend the dirhodium catalyst be miscible with one another or misciblewith the solvent in which the catalytic reaction is to be carried out.The choice of solvent(s), of course, will depend on a number of factorsincluding solubility of the solid support and/or dirhodium catalyst inthe solvent(s); possible side reactions between the solvent(s) and thesolid support, the dirhodium catalyst and other materials to be presentduring the catalytic reaction; difficulty of separating product from thesolvent(s); difficulty in drying the solvent (in cases where dry solventis needed); boiling point and/or decomposition point of the solventrelative to the temperature at which the catalytic is to be carried out;cost considerations; disposal considerations; and the like. Suitablesolvents include, for example, hydrocarbon solvents (e.g., hexanes andcyclohexane) and chlorinated hydrocarbons (e.g., chloroform andmethylene chloride), as well as aromatic solvents (e.g., toluene andxylenes).

[0071] Once the dirhodium catalyst and the solid support are provided,they are contacted with one another under conditions effective to bindthe dirhodium catalyst and the solid support together and to produce thedirhodium catalyst composition. This contact can take place at any timeprior to, during, or even subsequent to the catalytic reaction.Illustratively, the dirhodium catalyst and solid support can becontacted with one another prior to being mixed with the reactant(s) tobe catalyzed. Alternatively, the dirhodium catalyst can be premixed withthe reactant(s), and then this mixture can be contacted with the solidsupport. Still alternatively, the solid can be premixed with thereactant(s), and then this mixture can be contacted with the dirhodiumcatalyst. Still alternatively, the solid support can be premixed with aportion of the reactants, the dirhodium catalyst can be premixed withthe remainder of the reactants, and then the two mixtures can be mixedtogether, thus contacting the dirhodium catalyst and solid support withone another.

[0072] It should be understood that where the present applicationrecites a 2-step process of (i) providing a dirhodium catalystcomposition containing dirhodium catalyst (“DC”) bound together with asolid support (“SS”) and (ii) contacting this composition with someother material (“OM”), such as a reactant, step (i) can be performedfirst (e.g., by mixing DC and SS with each other) and then, in aseparate step (ii), contacting the resulting dirhodium catalystcomposition with OM. Alternatively, steps (i) and (ii) can be performedsimultaneously, for example, by first mixing DC and OM and thencontacting the DC/OM mixture with SS; by first mixing SS and OM and thencontacting the SS/OM mixture with DC; or by adding SS and DM separatelybut simultaneously to OM.

[0073] In one embodiment of the present invention, the dirhodiumcatalyst and the solid support are brought into contact with one anothereither prior to commencement of the reaction (e.g., prior to contactingthe catalyst with the reactant(s)) or shortly after the reaction hasbegun (e.g., before more than half of the expected yield of product isproduced). Although contacting the dirhodium catalyst and the solidsupport with one another late in the reaction (e.g., after more thanhalf of the expected yield of product is produced) or after the reactionis complete or substantially complete (e.g., after more than 90% of theexpected yield of product is produced), for example, by adding the solidsupport to the reaction mixture, may not be optimal, such a practicecan, nevertheless, be effective, for example, in facilitating separationof the dirhodium catalyst from the reaction mixture.

[0074] Details with respect to the temperature at which contact takesplace, the medium in which contact takes place, and the like do notappear to be particularly critical. Contacting the dirhodium catalystand the solid support at room temperature in methylene chloride hasproven to be suitable, although contact can be carried out at anytemperature from the freezing point to the boiling point of the solvent.

[0075] As alluded to above, “dirhodium catalyst composition”, as usedherein, is meant to refer to the composition in combination with one ormore other materials (e.g., in the presence of solvents, reactantsand/or products involved in the reaction to be catalyzed), substrates towhich the solid support may be bound, etc. However, it will beappreciated that, as used herein, “dirhodium catalyst composition” isalso meant to refer to the composition alone (without any othermaterials being present), as in the case where the dirhodium catalystcomposition is formed by contacting the dirhodium catalyst and solidsupport in the presence of a solvent followed by solvent removal (e.g.,by evaporation, filtration, centifugation, and/or decantation) or as inthe case where the dirhodium catalyst composition is separated from areaction mixture subsequent to completion of the reaction. In oneillustrative embodiment, the dirhodium catalyst composition is packedinto a column, said column then being useful for carrying one or more ofthe reactions discussed below, for example, by passing the reactantsthrough the column. After use in one such reaction, product, unusedreactant, by-products, etc., can be washed from the column usingsuitable solvents or combinations of solvents, and the column can bereused for the same or a different reaction. Such columns can be of anysuitable size. For example, micro columns containing the dirhodiumcatalyst composition can be used for running test reactions or foroptimizing reaction conditions.

[0076] The dirhodium catalyst compositions of the present invention canbe used in a variety of dirhodium catalyzed reactions. Briefly, theseinclude: insertion reactions (which are meant to include C—H insertions,Si—H insertions, O—H insertions, and N—H insertions) cyclopropanationreactions, annulations (which are meant to include [3+2] annulations and[3+4] annulations), and ω,ω-diarylalkanoate synthesis. These reactionscan be carried out under an inert atmosphere (e.g., argon gas) and/or inthe presence of a suitable drying agent, such as molecular sieves,sodium sulfate, magnesium sulfate, calcium sulfate, and the like.

[0077] For example, the method and composition of the present inventioncan be used in a variety of insertion reactions. One such insertionreaction relates to a method for producing a compound having the formula(“Formula XV”):

[0078] R¹, R², and R³ are independently selected from H, alkyl, aryl, orvinyl, or R¹ and R³, together with the atoms to which they are bonded,form a 5-12 membered ring, such as a cyclohexene ring, or acyclohexa-1,3-diene ring. The method can be used to prepare compounds inwhich R¹ and R³, together with the atoms to which they are bonded, forman aromatic ring, such as a substituted or unsubstituted phenyl ring,pyridine ring, thiophene ring, indole ring, etc. In the case where R¹and R³, together with the atoms to which they are bonded, form a phenylring, the compound produced by this method can have the formula(“Formula XVI”):

[0079] Y is an electron withdrawing group, examples of which includemoieties having the formulae: —C(O)R⁷⁷, —SO₂R⁷⁷, and —P(O)R⁷⁷R^(77′). Inthese formulae, each of R⁷⁷ and R^(77′) is independently selected froman alkyl group, an aryl group, and an alkoxy group. Illustratively, Ycan have the formula CO₂R¹² where R¹² is an alkyl group or an arylgroup.

[0080] X is CH₂, O or NR¹¹, and R¹¹ is H, an alkyl group, an aryl group,an acyl group, an alkoxycarbonyl group, or a silyl group having theformula —SiR³³R³⁴R³⁵, where R³³, R³⁴, and R³⁵ are independently selectedfrom an alkyl group and an aryl group.

[0081] Each of R³⁰ and R³¹ is independently selected from the groupconsisting of H, alkyl, aryl, and vinyl. R³² is an alkyl group, an arylgroup, an acyl group, an alkoxycarbonyl group, or a silyl group havingthe formula —SiR³⁶R³⁷R³⁸, where R³⁶, R³⁷, and R³⁸ are independentlyselected from an alkyl group and an aryl group. Alternatively, R³¹ andR³², together with the atoms to which they are bonded, can form a 5-12membered ring, such as a cyclopentyl or cyclohexyl ring (in the casewhere X is —CH₂), a piperidinyl ring (in the case where X is N), or atetrahydrofuranyl or a tetrahydropyranyl ring (in the case where X isO). Illustratively, this method is well-suited for forming compoundshaving Formula XV in which X is not CH₂ when each of R³⁰ and R³¹ is H.

[0082] The method includes providing a diazo compound having the formula(“Formula XVII”):

[0083] in which R¹, R², R³, and Y have the same meanings as given abovewith reference to Formula XV. The method further includes converting thediazo compound with a compound having the formula (“Formula XVIII”):

[0084] in the presence of a dirhodium catalyst composition of thepresent invention and under conditions effective to produce thecompound. In compound XVIII, R³⁰, R³¹, and R³² are defined as they areabove with regard to Formula XV. When, in the desired product, X is CH₂or O, X′ in Formula XVIII is CH₂ or O, respectively. When, in thedesired product, X is NR¹¹, X′ in Formula XVIII is NR^(11′) and R^(11′)is an alkyl group, an aryl group, an acyl group, an alkoxycarbonyl group(e.g., BOC or another alkoxycarbonyl amine protecting group), or a silylgroup (e.g., a triarylsilyl group, or a trialkylsilyl group).

[0085] Suitable dirhodium catalysts for carrying out the conversion ofXVII with XVIII are those having Formulae I-II and IV-XIV, as definedand discussed above. Other suitable dirhodium catalysts for carrying outthe conversion of XVII with XVIII are chiral dirhodium catalysts, suchas those having D₂ symmetry, for example, those which include a tworhodium atoms or ions that are bonded to one another along an axis andtwo carboxylate ligands, each of which two carboxylate ligands includestwo carboxylate groups bonded to each other via a moiety having FormulaIII. Such dirhodium catalysts are discussed in greater detail above.

[0086] Illustratively, the reaction can be carried out by contacting thecatalyst composition of the present invention with the compound ofFormula XVIII. In the case where the compound of Formula XVIII is aliquid (e.g., in the case where the compound of Formula XVIII istetrahydrofuran, tetrahydropyran, N-(tert-butyloxycarbonyl)pyrrolidine,N-(tert-butyloxycarbonyl)piperidine, cyclopentane, cyclohexane, etc.),this can be effected without the use of additional solvent.Alternatively, the mixture can be formed using an inert solvent or asolvent which is significantly less reactive toward the diazo compoundof Formula XVII than is the compound of Formula XVIII. As an example, ithas been found that when the compound of Formula XVIII istetrahydrofuran, the catalyst composition can be contacted with neattetrahydrofuran (i.e., using tetrahydrofuran as the solvent and withoutthe use of additional solvent), or hexanes can be used as a reactionmedium. The amount of catalyst used in this reaction can be about thesame as the amount of catalyst which would be employed if the catalystwere not bound on a solid support. For example, suitable mole ratios ofthe catalyst to the diazo compound of Formula XVII are: from about1:100,000 to about 1:20, such as from about 1:10,000 to about 1:50, fromabout 1:1000 to about 1:50, from about 1:500 to about 1:50, and/or fromabout 1:200 to about 1:100.

[0087] Once the catalyst composition is contacted with the compound ofFormula XVIII, the diazo compound of Formula XVII is added, for examplewith stirring. This addition can be carried out in a single portion,continuously, or batchwise. Slow, dropwise addition can be effected, forexample, using a syringe pump. The amount of diazo compound of FormulaXVII added is generally dependent on the amount of the compound ofFormula XVIII present in the reaction mixture. Illustratively, the moleratio of the compound of Formula XVIII to the diazo compound of FormulaXVII is from about 1:10 to about 10:1, such as from about 6:1 to about1:1 and/or from about 4:1 to about 2:1. The addition can be carried outat any suitable temperature from the freezing point to the boiling pointof the solvent and/or the compound of Formula XVIII. For example, theaddition can be carried out from about −50° C. to about 60° C. Roomtemperature addition and addition at about 10° C. are illustrative.Illustratively, in one embodiment of the present invention wherediastereomerically and/or enantiomerically pure product is desired,reaction conditions can be optimized by adjusting the additiontemperature. Although not intending to be limitative in any way on thescope of the present invention, it is believed that (i) formation ofdiastereomerically and/or enantiomerically pure product can be favoredby lower addition temperatures (e.g., from about −50° C. to about 10°C.); and (ii) yield and improved diastereoisomeric and/or enantiomericpurity can be improved by performing the reaction substantially in theabsence of oxygen. As used herein, “substantially in the absence ofoxygen” means that the liquid reactants and solvents (if any) employedin carrying out the reaction are degassed, for example by bubbling aninert gas (e.g., nitrogen or argon) therethrough, that the reaction iscarried out under blanket of inert gas, and that all transfers(subsequent to degassing) are carried out such that ambient air isexcluded (e.g., by using rubber septums, gas tight syringes, and thelike).

[0088] The conversion of the compound of Formula XVII with a compound ofFormula XVIII to produce either or both diastereomers of a compound ofFormula XV described above can be used for preparing compounds havingthe formula (“Formula XIX”):

[0089] In this case, the conversion of the diazo compound of FormulaXVII is carried out with a cyclic compound having the formula (“FormulaXX”):

[0090] in which X′ is defined as above and n is 3-10. In oneillustrative embodiment, R¹ and R³, together with the atoms to whichthey are bonded, form a phenyl ring, and Y has the formula —CO₂R¹⁰ whereR¹⁰ is an alkyl or aryl group. The method can be used for makingcompounds in which X is NR¹¹ and in which n is 3 or 4. The method isalso suitable for making compounds having the formulae (“Formula XXI-A”and “Formula XXI-B”, respectively):

[0091] in which case the dirhodium catalyst employed is a chiraldirhodium catalyst. For example, by using the S-isomer of compoundshaving Formulae IV-XII, as defined and discussed above, compounds ofFormula XXI-B which are substantially enantiomerically pure (e.g., >80%ee, >90% ee, >95% ee, >98% ee, and/or >99% ee) can be prepared. Examplesof compounds having Formula XXI-A and XXI-B include those in which X isNR¹¹, n is 3 or 4, Y is CO₂R¹², R¹² is alkyl or aryl, and R¹ and R³,together with the atoms to which they are bonded, form an aromatic ring,such as those compounds of Formulae XXI-A or XXI-B in which X is NH, R¹²is a methyl group, and R¹ and R³, together with the atoms to which theyare bonded, form a phenyl ring.

[0092] Such compounds can have one of the following formulae (“FormulaXXII-A” and “Formula XXII-B”, respectively):

[0093] or one of the following formulae (“Formula XXII-C” and “FormulaXXII-D”, respectively):

[0094] the latter of which is also referred to as threo methylphenidateand which is believed to be the biologically active form of RITALIN™.Where stereospecifcity is not important, racemic mixtures of compoundshaving Formulae IV-XII or other dirhodium tetracarboxylates can beemployed in the method and/or composition of the present invention toproduce the racemic methylphenidate.

[0095] The method of the present invention can also be used to preparecompounds having Formula XV in which X is NR¹¹ and in which R³¹ and R³²,together with the atoms to which they are bonded, represent a ringhaving the formula (“Formula XXIII”):

[0096] where R³⁰ is H. That is, the method can be used to preparecompounds having the formula (“Formula XXIV”):

[0097] In these formulae, R⁴¹, R⁴², and R⁴³ are independently selectedfrom H, alkyl, aryl, or vinyl, or R⁴¹ and R⁴³, together with the atomsto which they are bonded, form a 5-12 membered ring. Y′ is an electronwithdrawing group, for example, the electron withdrawing groupsdiscussed above with regard to Y, and m is 2-9. The reaction involvesproviding a diazo compound having Formula XVII and converting the diazocompound with a cyclic amine having the formula (“Formula XXV”):

[0098] in the presence of a dirhodium catalyst composition of thepresent invention and under conditions effective to produce thecompound. Suitable conditions for this reaction are the same as the onesdiscussed above with regard to the conversion of compounds of FormulaXVII with compounds of Formula XVIII. By using a chiral catalyst,compounds having the formula (“Formula XXVI”):

[0099] can be produced.

[0100] A variety of methods can be used to prepare the cyclic aminehaving Formula XXV, such as the method that is described above withregard to preparing compounds having Formula XIX using diazo compoundsof Formula XVII, cyclic compounds of Formula XX, and a dirhodiumcatalyst composition of the present invention. Rather than running thereaction in two steps (i.e., by first reacting a diazo compounds ofFormula XVII with a cyclic compound of Formula XX in which X is N toproduce a cyclic amine having Formula XIX and then reacting the cyclicamine having Formula XIX with a diazo compound having Formula XVII toproduce the desired compound of Formula XXIV), the reaction can becarried out in a single step by, for example, by contacting the cycliccompound of Formula XX in which X is N with at least two equivalents ofa diazo compound of Formula XVII. Reaction conditions suitable forcarrying out this one step reaction include those discussed above withregard to the two step method. Illustratively, during the first part ofthe reaction (i.e., during the addition of the first half of the diazocompound having Formula XVII), the reaction is carried out with cooling(e.g., from about −50° C. to about 0° C.). Then the reaction mixture iswarmed, and the second part of the reaction (i.e., during the additionof the second half of the diazo compound having Formula XVII) is carriedout at elevated temperatures (e.g., from about 20° C. to about 100° C.).Alkanes having melting points of less than about −50° C. and boilingpoints greater than about 60° C. are the suitable solvents for thisreaction, but the nature of the solvent is not particularly critical andalternatives can be used.

[0101] The compounds prepared by the above method (i.e., compoundshaving Formulae XV, XVI, XIX, XXI-A, XXI-B, XXII-A, XXII-B, XXII-C,XXII-D, XXIV, and XXVI) are appropriately functionalized for furtherconversion by, for example, ester reduction or Grignard addition tohighly functionalized bases. In the case where a chiral catalyst isemployed, e.g., the S-isomer of compounds having Formulae IV-XII, asdefined and discussed above, these compounds can be used as C₂ symmetricbases, or, as indicated above, they can be further converted (e.g., byester reduction or Grignard addition) to highly functionalized C₂ bases.C₂ bases are very useful for controlling stereochemistry in organicsynthesis, for example, as described in Takahata et al., “New Entry toC2 Symmetric Trans-2,6-bis(hydroxymethyl)piperidine Derivatives Via theSharpless Asymmetric Dihydroxylation,” Tetrahedron-Asymmetry,6:1085-1088 (1995) and in Bennani et al., “Trans-1,2-diaminocyclohexaneDerivatives as Chiral Reagents, Scaffolds, and Ligands forCatalysis—Applications in Asymmetric Synthesis and MolecularRecognition,” Chemical Reviews, 97:3161-3195 (1997), which are herebyincorporated by reference.

[0102] Further examples and details of using dirhodium catalysts toeffect insertions can be found, for example, in Davies et al.,“Catalytic Asymmetric C—H Activation of Silyl Enol Ethers as anEquivalent of an Asymmetric Michael Reaction,” J. Am. Chem. Soc.,123(9):2070-2071 (2001); Davies et al., “Kinetic Resolution and DoubleStereodifferentiation in Catalytic Asymmetric C—H Activation of2-Substituted Pyrrolidines,” Organic Letters, 3(11):1773-1775 (2001);Davies et al., “Asymmetric Intramolecular C—H Insertions ofAryldiazoacetates,” Organic Letters, 3(10):1475-1477 (2001); CatalyticAsymmetric C—H Activation of Alkanes and Tetrahydrofuran,” J. Am. Chem.Soc., 122(13):3063-3070 (2000); Davies et al., “Highly Regio-,Diastereo-, and Enantioselective C—H Insertions of MethylAryldiazoacetates into Cyclic N-Boc—Protected Amines. AsymmetricSynthesis of Novel C₂-Symmetric Amines and threo-Methylphenidate,” J.Am. Chem Soc., 121(27):6509-6510 (1999); Davies et al., “CatalyticAsymmetric Synthesis of Syn-Aldol Products from Intermolecular C—HInsertions Between Allyl Silyl Ethers and Methyl Aryldiazoacetates,”Organic Letters, 1(3):383-385 (1999); Davies, “Rhodium—StabilizedVinylcarbenoid Intermediates in Organic Synthesis,” Current OrganicChemistry, 2:463-488 (1998); Davies et al., “Recent Progress inAsymmetric Intermolecular C—H Activation by Rhodium CarbenoidIntermediates,” Journal of Organometallic Chemistry, 617-618:47-55(2001); Davies, “Dirhodium Tetra(N-arylsulfonylprolinates) as ChiralCatalysts For Asymmetric Transformations of Vinyl- andAryldiazoacetates,” Eur. J. Org. Chem., pages 2459-2469 (1999); Davies,“Asymmetric Synthesis Using Rhodium-Stabilized VinylcarbenoidIntermediates,” Aldrichimica Acta, 30(4):107-114 (1997); U.S. Pat. No.6,410,746 to Davies; and International Publication No. WO 00/64583.Collectively, these references are referred to herein as the “InsertionReferences”, and each of these references is hereby incorporated byreference. The reactions set forth in the Insertion References and otherreferences relating to dirhodium catalyzed insertion reactions can becarried out using the dirhodium catalyst composition of the presentinvention in place of the dirhodium catalysts described in the InsertionReferences. The amount and type of catalyst used in this reaction can beabout the same as the amount and type of catalyst which would beemployed if the catalyst were not bound on a solid support. Suitabletypes and amounts of catalyst include those specified hereinabove.

[0103] The method and composition of the present invention can also beused in connection with other insertion reactions, as well as withcyclopropanation reactions. Such other insertion reactions and suchcyclopropanation reactions are illustrated by the following method forproducing a compound having the formula (“Formula XXVII”):

[0104] In Formula XXVII, R¹, R², and R³ are independently selected fromH, alkyl, aryl, or vinyl, or R¹ and R³, together with the atoms to whichthey are bonded, form a 5-12 membered ring. Y is an electron withdrawinggroup (e.g., an ester group). R¹³¹ is H, and R¹³⁰ is an alkyl group, anaryl group, an alkoxy group, an amine group, or a silyl group; or R¹³⁰and R¹³¹, together with the atom to which they are bonded, form asubstituted or unsubstituted cyclopropane moiety. The method includesproviding a diazo compound having the formula (“Formula XXVIII”):

[0105] (in which R¹, R², R³, and Y are defined as they are above withregard to Formula XXVII) and converting the diazo compound of FormulaXXVIII to the compound of Formula XXVII in the presence of a dirhodiumcatalyst composition of the present invention and under conditionseffective to produce the compound of Formula XXVII.

[0106] In cases where R¹³¹ is H, and R¹³⁰ is an alkyl group, an arylgroup, an alkoxy group, an amine group, or a silyl group, this reactionis a C—H, C—O, C—N, or C—Si insertion, and suitable reactants foreffecting the conversion of the diazo compound of Formula XXVIII to thecompound of Formula XXVII can be readily ascertained by one skilled inthe art. Examples of such reactions are set forth in the InsertionReferences, and each of these references is hereby incorporated byreference. The reactions set forth in the Insertion References and otherreferences relating to dirhodium catalyzed insertion reactions can becarried out using the dirhodium catalyst composition of the presentinvention in place of the dirhodium catalysts described in the InsertionReferences. To carry out the C—H, C—O, C—N, or C—Si insertion reactionsrepresented by the conversion of the diazo compound of Formula XXVIII tothe compound of Formula XXVII, the amount of catalyst can be about thesame as the amount of catalyst which would be employed if the catalystwere not bound on a solid support. For example, suitable mole ratios ofthe catalyst to the diazo compound of Formula XXVIII are from about1:100,000 to about 1:20, such as from about 1:10,000 to about 1:50, fromabout 1:1000 to about 1:50, from about 1:500 to about 1:50, and/or fromabout 1:200 to about 1:100.

[0107] The above-described insertion reactions exemplify the presentinvention's usefulness in catalyzing aryldiazomethane orvinyldiazomethane insertion reactions in which aryldiazomethanes orvinyldiazomethanes are contacted with a dirhodium catalyst compositionaccording to the present invention under conditions effective tocatalyze the aryldiazomethane or vinyldiazomethane insertion reaction.These methods provide new and useful ways to make compounds (such as thecompounds illustrated by Formulae XV, XVI, XIX, XXI-A, XXI-B, XXII-A,XXII-B, XXII-C, XXII-D, XXIV, XXVI, and XXVII (in cases where R¹³¹ isH)) and to produce C—H bonds.

[0108] In cases where R¹³⁰ and R¹³¹, together with the atom to whichthey are bonded, form a substituted or unsubstituted cyclopropanemoiety, the compound of Formula XXVII can have the formula (“FormulaXXIX”):

[0109] Such reactions are commonly referred to as cyclopropanationreactions. In Formula XXIX, each of R¹³², R¹³³, and R¹³⁴ canindependently represent H, an alkyl group, an aryl group, a silyloxygroup, an alkoxy group, a halogen, an amine group, or an alkyl or arylthiol group. Alternatively, R¹³² and R¹³³, together with the atoms towhich they are bonded, can form a 4-12 membered ring. Stillalternatively, R¹³³ and R¹³⁴, together with the atom to which they arebonded, can form a 3-12 membered ring. Compounds of Formula XXIX can beproduced by converting the diazo compound of Formula XXVIII using acompound having the formula (“Formula XXX”):

[0110] in which R¹³², R¹³³, and R¹³⁴ are defined as they are above withregard to Formula XXIX. The reaction is carried out using a dirhodiumcatalyst composition of the present invention. Other reaction conditionssuitable for carrying out this conversion are the same as thosediscussed above with regard to insertion reactions. The amount ofcatalyst used in this reaction can be about the same as the amount ofcatalyst which would be employed if the catalyst were not bound on asolid support. For example, suitable mole ratios of the catalyst to thediazo compound of Formula XXVIII are: from about 1:100,000 to about1:20, such as from about 1:10,000 to about 1:50, from about 1:1000 toabout 1:50, from about 1:500 to about 1:50, and/or from about 1:200 toabout 1:100.

[0111] Once formed, compounds of Formula XXIX can be used in an numberof ways.

[0112] For example, compounds of Formula XXIX in which at least one ofR¹ and R² is H and in which R¹³² is an electron donating group can beconverted to cyclopentenes, for example, by treating the compound ofFormula XXIX with a Lewis acid, such as diethyl aluminum chloride. Asused herein, “electron donating group” refers to those groups which areable to inject electron density from adjacent positions in a molecule,as determined, for example, by reference to the classificationestablished by the Hammett scale, such as the one set forth in Gordon,which is hereby incorporated by reference. Suitable electron-donatinggroups include those having a para a value less that or equal to aboutzero (e.g., less that or equal to about −1, and/or less that or equal toabout −2 with reference to the Hammett scale. Particular examples ofelectron withdrawing groups are alkoxy groups.

[0113] Alternatively, compounds of Formula XXIX in which R¹ and R² areH, in which R¹³² is an electron donating group (e.g., an alkoxy group),and in which R³ is a silyloxy group can be converted to dihydrofurans,for example, by treating the compound of Formula XXIX with a fluoride,such as tetrabutylammonium fluoride.

[0114] Still alternatively, compounds of Formula XXIX in which at leastone of R¹ and R² is H, in which R¹³² is an electron donating group(e.g., an alkoxy group), in which Y is a carboxylic acid ester of theformula —COOR¹⁶⁰, and in which R¹⁶⁰ is a tertiary alkyl moiety (e.g., at-butyl group) can be converted to butenolides, for example, by treatingthe compound of Formula XXIX with a Lewis acid catalyst, such a boronhalide (e.g., BF₃ or BBr₃) or another Lewis acid catalyst containingboron.

[0115] Compounds of Formula XXIX can also be used to prepare compoundshaving the formula (“Formula XXXI”);

[0116] where each of R¹³², R¹³³ R¹³⁴, and Y are defined as they werewith regard to Formula XXIX and where R¹³⁵ is a carboxylic acid group, acarboxylic acid derivative (e.g., a carboxylic acid ester, a carboxylicacid amide, etc.), or an amino group (e.g., a unsubstituted,monosubstituted, or disubstituted amino group). The conversion ofcompounds of Formula XXIX to compounds of Formula XXXI in which R¹³⁵ isa carboxylic acid or carboxylic acid derivative can be effected, forexample, by treating the compound of Formula XXIX with an oxidativealkene cleavage reagent, such as RuCl₃/NaIO₄. Compounds of Formula XXXIin which R¹³⁵ is a carboxylic acid or carboxylic acid derivative can befurther converted to compounds of Formula XXXI in which R¹³⁵ is an aminogroup, for example by treatment with triethylamine, diphenylphosphorylazide, and t-butyl alcohol; followed by treatment with di-t-butyldicarbonate to produce a Boc-protected amine; and conversion of theBoc-protected amine to the free amine using, for example, strong acid(e.g., 3 N HCl in EtOAc). Using this method in conjunction withenantiomerically pure compounds of Formula XXIX (formed, for example, byusing a dirhodium catalyst composition of the present inventioncontaining a diastereomerically pure dirhodium catalyst), each of thefour stereoisomers of 2-phenylcyclopropan-l-amino acid can be produced.

[0117] Compounds of Formula XXIX can also be converted to compoundshaving the formula (“Formula XXXII”):

[0118] where each of R¹, R², R³, R¹³², R¹³³, and R¹³⁴ are defined asthey were with regard to Formula XXIX and where Y′ is an alkyl group, analdehyde group, a ketone, or a vinyl group. As one illustrative example,R² can be H; R¹ and R³, together with the atoms to which they arebonded, can form a phenyl group; R¹³² can be H; R¹³³ can be a4-alkoxyphenyl group; R¹³⁴ can be a phenyl group; Y can be a carboxylicacid ester; and Y′ can be an aldehyde group, a hydroxymethyl group, avinyl group, or an ethyl group. Compounds of Formula XXIX can beconverted to a compound of Formula XXXII where Y′ is a hydroxymethylgroup by treating the compound of Formula XXIX with a reducing agent,e.g., LiAlH₄, in an inert solvent (e.g., tetrahydrofuran) at anappropriate temperature (e.g. from about −78° C. to about 0° C.). Theresulting alcohol can then be oxidized (e.g., under Swern conditions) toproduce the compound of Formula XXXII where Y′ is an aldehyde group. Thealdehyde can then be converted to the corresponding alkene (i.e., acompound of Formula XXXII where Y′ is a vinyl group), for example, bytreatment with Ph₃P═CH₂. The alkene can then be hydrogenated (e.g.,using Rh/Al₂O₃) to produce a compound of Formula XXXII where Y′ is anethyl group. For example, using this sequence of reactions inconjunction with a compounds of Formula XXIX in which R¹ and R³, takentogether with the atoms to which they are bonded, represent a phenylring; in which R¹³³ is a phenyl group; and in which R¹³⁴ is a4-(2-chloroethoxy)phenyl group, and further treatment of the resultingcompound of Formula XXXII where Y′ is an ethyl group with dimethylaminein the presence of sodium iodide in DMF-H₂O at appropriate temperature(e.g., about 55° C.), a cyclopropyl analog of tamoxifen can be produced.Using this method in conjunction with enantiomerically pure compounds ofFormula XXIX (formed, for example, by using a dirhodium catalystcomposition of the present invention containing a diastereomericallypure dirhodium catalyst), the stereochemistry of the chiral centers inthis tamoxifen analog can be controlled. Further details regarding theconversion of Compounds of Formula XXIX to compounds of Formula XXXIIcan be found, for example, in Davies et al., “Stereoselectivity ofMethyl Aryldiazoacetate Cyclopropanations of 1,1-Diarylethylene.Asymmetric Synthesis of a Cyclopropyl Analogue of Tamoxifen,” OrganicLetters, 2(6):823-826 (2000), which is hereby incorporated by reference.

[0119] Compounds of Formula XXXI can also be used to synthesizecompounds having the formula (“Formula XXXIII”):

[0120] where each R¹³², R¹³³, R¹³⁴ and Y are defined as they were withregard to Formula XXXI; where R¹³⁵ is a carboxylic acid group or acarboxylic acid derivative; and where R¹³⁶ represents an aryl group oran alkyl group. The synthesis includes providing a compound havingFormula XXXI in which R¹³⁵ is a carboxylic acid group or a carboxylicacid derivative and converting this compound of Formula XXXI to thecompound of Formula XXXIII using, for example, an aryl or alkyl cuprate(e.g., having the formula [R¹³⁶₂CuLi₂CN).

[0121] Compounds of Formula XXXIII in which R¹³⁵ is a carboxylic acidgroup or a carboxylic acid derivative and in which R¹³² has the formula:

[0122] where each R¹³⁹ independently represents an alkyl group, an arylgroup, a halogen, a hydroxy group, an amino group, a thiol group, analkyl thiol group, an aryl thiol group or two or more of R¹³⁹, togetherwith that atoms to which they are bonded, form a 5-12 membered ring; andwhere p represents an integer from 0 to 4 can be converted to compoundshaving the formula (“Formula XXXIV”):

[0123] where each of R¹³³, R¹³⁴, and R¹³⁶ is defined as it was withregard to Formula XXXIII; where R¹³⁷ is H and R¹³⁸ represents an aminogroup or R¹³⁷ and R¹³⁸, together with the carbon atom to which they arebonded, represent a carbonyl moiety; and where R¹³⁹ is defined as above.For example, compounds of Formula XXXIII can be decarboxylated and thenacylated (e.g., using a Friedel Crafts acylation method) to producecompounds of Formula XXXIV where R¹³⁷ and R¹³⁸, together with the carbonatom to which they are bonded, represent a carbonyl moiety. Reductiveamination can be used to convert R¹³⁷ and R¹³⁸ from a ═O group to anamine group.

[0124] Further details with regard to the aforementionedcyclopropanation reactions and the reactions which use the products ofthese cyclopropanation reactions can be found, for example, in Davies etal., “Asymmetric Cyclopropanations by Rhodium (II)N-(Arylsulfonyl)prolinate Catalyzed Decomposition of Vinyldiazomethanesin the Presence of Alkenes. Enantioselective Synthesis of the FourStereoisomers of 2-Phenylcyclopropan-1-amino Acid,” J. Am. Chem. Soc.,118(29):6897-6907 (1996); Davies et al., “Stereoselectivity of MethylAryldiazoacetate Cyclopropanations of 1,1-Diarylethylene. AsymmetricSynthesis of a Cyclopropyl Analogue of Tamoxifen,” Organic Letters,2(6):823-826 (2000); Davies et al., “Effect of Diazoalkane Structure onthe Stereoselectivity of Rhodium(II) (S)-N-(Arylsulfonyl)prolinateCatalyzed Cyclopropanations,” Tetrahedron Letters, 37(24):4133-4136(1996); Davies et al., “Effect of Catalyst on the Diastereoselectivityof Methyl Phenyldiazoacetate Cyclopropanations,” Tetrahedron Letters,39:8811-8812 (1998); Davies et al., “Enantioselective Synthesis of FusedCycloheptadienes by a Tandem Intramolecular Cyclopropanation/CopeRearrangement Sequence,” J. Org. Chem., 64(23):8501-8508 (1999); Davies,“Rhodium-Stabilized Vinylcarbenoid Intermediates in Organic Synthesis,”Current Organic Chemistry, 2:463-488 (1998); Davies et al., “Effect ofRhodium Carbenoid Structure on Cyclopropanation Chemoselectivity,”Tetrahedron, 56:4871-4880 (2000); Davies, “DirhodiumTetra(N-arylsulfonylprolinates) as Chiral Catalysts For AsymmetricTransformations of Vinyl- and Aryldiazoacetates,” Eur. J. Org. Chem.,pages 2459-2469 (1999); Nagashima et al., “Catalytic AsymmetricSolid-Phase Cyclopropanation,” J. Am. Chem. Soc., 123(11):2695-2696(2001); and Davies, “Asymmetric Synthesis Using Rhodium—StabilizedVinylcarbenoid Intermediates,” Aldrichimica Acta, 30(4):107-114 (1997),each of which is hereby incorporated by reference. All of thecyclopropanation reactions set forth in the above-identified referencescan be modified by using the method and dirhodium catalyst compositionsof the present invention. Illustratively, the dirhodium catalystcomposition of the present invention can contain about the same amountof dirhodium catalyst as called for in these references.

[0125] The above-described reactions exemplify the present invention'susefulness in catalyzing aryldiazomethane or vinyldiazomethanecyclopropanation reactions in which aryldiazomethanes orvinyldiazomethanes are contacted with a dirhodium catalyst compositionaccording to the present invention under conditions effective tocatalyze the aryldiazomethane or vinyldiazomethane cyclopropanationreaction. These methods provide new and useful ways to make compounds(such as the compounds illustrated by Formulae XXVII (in cases whereR¹³⁰, R¹³⁰, and the carbon to which they are bonded form a cyclopropanemoiety), XXIX, and XXXI-XXXIV) and to produce C—C bonds.

[0126] The method and composition of the present invention can also beused to produce optionally substituted cycloheptadienes or optionallysubstituted bicyclooctadienes. In this method, a diazo compound havingthe formula (“Formula XXXV”):

[0127] is provided. In Formula XXXV, Y is an electron withdrawing group;and R¹, R², and R³ are independently selected from H, alkyl, aryl,silyloxy, or vinyl, or R¹ and R³, together with the atoms to which theyare bonded, form a 5-12 membered ring. The diazo compound having theFormula XXXV is then converted with a optionally substituted homocyclic,heterocyclic, or non-cyclic diene. Suitable optionally substitutedhomocyclic, heterocyclic, or non-cyclic diene include those having theformula (“Formula XXXVI”):

[0128] In Formula XXXVI, each of R¹⁴⁴, R¹⁴⁶, R¹⁴⁷, and R¹⁴⁸independently represent an alkyl group, an aryl group, an alkoxy group,a halogen, hydrogen, an acyl group, a hydroxy group, a thiol group, analkyl thiol or aryl thiol group, a carboxylic acid group, a carboxylicacid derivative, or a silyloxy group, or two or more of R¹⁴⁴, R¹⁴⁶,R¹⁴⁷, and R¹⁴⁸, together with the atom or atoms to which they arebonded, form a 5-12 membered ring. Each of R¹⁴³ and R¹⁴⁵ independentlyrepresents an alkyl group, an aryl group, an alkoxy group, a halogen,hydrogen, an acyl group, a hydroxy group, a thiol group, an alkyl thiolor aryl thiol group, a carboxylic acid group, a carboxylic acidderivative, or a silyloxy group, or R¹⁴³ and R¹⁴⁵ together represent a—O— moiety, a —S— moiety, a substituted or unsubstituted bivalent aminomoiety (e.g., a substituted or unsubstituted bivalent amino moietyhaving the formula —N(R¹⁵⁰)— in which R¹⁵⁰ is H, an aryl group, or alkylgroup), or a substituted or unsubstituted methylene or ethylene moiety.Examples of optionally substituted cycloheptadienes or optionallysubstituted bicyclooctadienes that can be produced using this methodinclude optionally substituted cyclohepta-1,5 dienes and optionallysubstituted 8-aza-bicyclo [3.2.1]octa-2,6 dienes, such as those havingthe formula (“Formula XXXVII”):

[0129] in which R¹⁴³, R¹⁴⁴, R¹⁴⁵, R¹⁴⁶, R¹⁴⁷, and R¹⁴⁸ have the samemeanings as set forth above with regard to Formula XXXVI and in whichR¹, R², R³, and Y have the same meanings as set forth above with regardto Formula XXXV. The reaction is carried out using a dirhodium catalystcomposition of the present invention. Other reaction conditions suitablefor carrying out the conversion of compounds having Formula XXXV withoptionally substituted homocyclic, heterocyclic, or non-cyclic diene arethe same as those discussed above with regard to insertion reactions.The amount of catalyst used in this reaction can be about the same asthe amount of catalyst which would be employed if the catalyst were notbound on a solid support. For example, suitable mole ratios of thecatalyst to the diazo compound of Formula XXXV are: from about 1:100,000to about 1:20, such as from about 1:10,000 to about 1:50, from about1:1000 to about 1:50, from about 1:500 to about 1:50, and/or from about1:200 to about 1:100. These reactions can be carried outstereospecifically, for example with enantiomerically pure dirhodiumcatalysts (such as enantiomerically pure dirhodium catalysts having D₂symmetry), such as those depicted in Formulae IV and VII-XII.Alternatively, the reaction can be carried out racemically, in whichcase any dirhodium tetracarboxylate catalyst can be employed.

[0130] Compounds of Formula XXXVII in which R¹⁴ ³ and R¹⁴⁵ togetherrepresent a substituted or unsubstituted bivalent amino moiety havingthe formula —N(R¹⁵⁰)— (in which R¹⁵⁰ is H, an aryl group, or alkylgroup) can be readily converted to 3-aryltropanes, for example byreaction the compound of Formula XXXVII with a Grignard reagent (e.g.,having the formula R¹⁵¹—Mg—X, where R¹⁵¹ is an aryl group and X is ahalogen). Illustratively, the 3-aryltropane can have the formula(“Formula XXXVIII”):

[0131] where R¹⁵¹ is H, an aryl group, or an alkyl group; R¹⁵² is anaryl group; R¹⁵³ represents H or a C1-C12 ketone; and R¹⁵⁴ represents Hor a C1-C12 ketone. Further details regarding the dirhodium catalyzedpreparation of cycloheptadienes and bicyclooctadienes, as well as theproduction of tropanes and other useful materials from thesecycloheptadienes and bicyclooctadienes are available in U.S. Pat. No.5,760,055 to Davies; U.S. Pat. No. 5,591,854 to Davies; Davies, “[3+4]Annulations Between Rhodium—Stabilized Vinylcarbenoids and Dienes,”Advances in Cycloaddition, 5:119-164 (1999); Davies et al., “TandemAsymmetric Cyclopropanation/Cope Rearrangement. A HighlyDiastereoselective and Enantioselective Method for the Construction of1,4-Cycloheptadienes,” J. Am. Chem. Soc., 120(4):3326-3331 (1998);Davies et al., “Enantioselective Synthesis of Functionalized Tropanes byRhodium(II) Carboxylate-Catalyzed Decomposition of Vinyldiazomethanes inthe Presence of Pyrroles,” J. Org. Chem., 62(4):1095-1105 (1997); Davieset al., “Effect of Rhodium Carbenoid Structure on CyclopropanationChemoselectivity,” Tetrahedron, 56:4871-4880 (2000); Davies et al.,“Enantioselective Synthesis of Fused Cycloheptadienes by a TandemIntramolecular Cyclopropanation/Cope Rearrangement Sequence,” J. Org.Chem., 64(23):8501-8508 (1999); Davies, “Rhodium—StabilizedVinylcarbenoid Intermediates in Organic Synthesis,” Current OrganicChemistry, 2:463-488 (1998); and Davies, “Asymmetric Synthesis UsingRhodium—Stabilized Vinylcarbenoid Intermediates,” Aldrichimica Acta,30(4):107-114 (1997), each of which is hereby incorporated by reference.

[0132] The above-described reactions exemplify the present invention'susefulness in catalyzing [3+4] annulation reactions in whichvinyldiazomethanes are reacted, for example, intermolecularly with adiene by contacting the vinyldiazomethane with a dirhodium catalystcomposition of the present invention under conditions effective toproduce a seven or eight membered ring or ring system. It should benoted that these reactions can also be carried out intramolecularly witha diene moiety contained in the vinyldiazomethane. These methods providenew and useful ways to make compounds (such as the compounds illustratedby Formulae XXXVII and XXXVIII) and to produce seven or eight memberedrings and/or seven or eight membered ring systems (e.g.,bicyclooctadiene ring systems).

[0133] The method and composition of the present invention can also beused to produce a compound having the formula (“Formula XXXIX”):

[0134] In Formula XXXIX, R¹, R², and R³ are independently selected fromH, alkyl, aryl, or vinyl, or R¹ and R³, together with the atoms to whichthey are bonded, form a 5-12 membered ring, such as a cyclohexene ring,or a cyclohexa-1,3-diene ring. Illustratively, the method can be used toprepare compounds in which R¹ and R³, together with the atoms to whichthey are bonded, form an aromatic ring, such as a 3,4-dichlorophenylring, in which case the compound produced can have the formula (“FormulaXL”):

[0135] in which Y is an electron withdrawing group, examples of whichinclude moieties having the formulae: —C(O)R⁷⁷, —SO₂R⁷⁷, and—P(O)R⁷⁷R⁷⁷. In these formulae, each of R⁷⁷ and R^(77′) is independentlyselected from an alkyl group, an aryl group, and an alkoxy group. Forexample, Y can have the formula CO₂R¹² where R¹² is an alkyl group or anaryl group.

[0136] Each of R⁵⁴, R⁵⁵, R⁵⁶, R⁵⁷, R⁵⁸, and R⁵⁹ is independentlyselected from the group consisting of H, alkyl, aryl, halogen, andalkoxy.

[0137] The method includes providing a 1,3-cyclohexadiene having theformula (“Formula XLI”):

[0138] where R⁵⁴, R⁵⁵, R⁵⁶, R⁵⁷, R⁵⁸, and R⁵⁹ are defined as above withregard to Formula XL. The method further includes converting the1,3-cyclohexadiene with a diazo compound having the formula (“FormulaXLII”):

[0139] in which Y, R¹, R², and R³ are as defined above in the presenceof a rhodium catalyst composition of the present invention.

[0140] Illustratively, the reaction can be carried out by contacting thecatalyst composition with the 1,3-cyclohexadiene of Formula XLI.Alternatively, the catalyst composition can be first contacted with thediazo compound of Formula XLII. Still alternatively, the1,3-cyclohexadiene of Formula XLI can first be combined with the diazocompound of Formula XLII, and then the catalyst composition can becontacted with this combination. In the case where the1,3-cyclohexadiene of Formula XLI is a liquid (e.g., in the case wherethe compound of Formula XLI is 1,3-cyclohexadiene), the reaction can becarried out without the use of additional solvent. Alternatively, themixture can be formed using an inert solvent or a solvent which issignificantly less reactive towards the diazo compound of Formula XLIIthan is the compound of Formula XLI. Suitable solvents include alkanes,such as hexanes. The solvent can be dried prior to use usingconventional methods; and the reaction vessel can also be dried, such asby flaming or in an oven. The amount of catalyst used in this reactioncan be about the same as the amount of catalyst which would be employedif the catalyst were not bound on a solid support. For example, suitablemole ratios of the catalyst to the diazo compound of Formula XLII are:from about 1:100,000 to about 1:20, such as from about 1:10,000 to about1:50, from about 1:1000 to about 1:50, from about 1:500 to about 1:50,and/or from about 1:200 to about 1:100.

[0141] Once the catalyst composition is contacted with the compound ofFormula XLI, the compound of Formula XLII is added, for example withstirring. Addition can be carried out in a single portion, continuously,or batchwise. Slow, dropwise can be effected, for example, by using asyringe pump. The amount of compound of Formula XLII added is generallydependent on the amount of compound of Formula XLI present in thereaction mixture. For example, the mole ratio of compound of FormulaXLII to compound of Formula XLI can be from about 1:10 to about 10:1,such as from about 1:8 to about 1:1 and/or from about 1:6 to about 1:4.The addition can be carried out at any suitable temperature from thefreezing point to the boiling point of the solvent and/or the compoundof Formula XLI. Illustratively, the addition can be carried out fromabout −50° C. to about 60° C., such as at about room temperature. Incertain embodiments, higher temperatures may favor a reverse Coperearrangement, in which case, compounds having Formula XXXIX rearrangeto form compounds having the formula (“Formula XLIII”):

[0142] The method is suitable for making compounds having Formula XLwhich are substantially enantiomerically pure, such as, for example,compounds having the formula (“Formula XLIV”):

[0143] such as compounds having the formula (“Formula XLV”):

[0144] In one embodiment of the present invention, a substantiallyenantiomerically selective reaction is desired, and a chiral catalyst,such as one having D₂ symmetry, is employed. For example, by using oneof the catalysts depicted in Formulae IV and VII-XII, compounds ofFormulae XLIV and XLV which are substantially enantiomerically pure(e.g., >80% ee, >90% ee, >95% ee, >98% ee, and/or >99% ee) can beprepared.

[0145] The cyclohexadiene derivative of Formula XXXIX wherein R⁵⁷ is Hcan be converted into a compound having the formula (“Formula XLVI”):

[0146] in which R¹, R², R³, R⁵⁴, R⁵⁵, R⁵⁶, R⁵⁸, R⁵⁹, and Y are definedas they were above for the compounds having Formula XXXIX. Theconversion can be carried out with hydrogenating and oxidizing agentsunder conditions effective to form the compound of Formula XLVI. Thehydrogenation and oxidation reactions can be carried out simultaneouslyor sequentially, and, when carried out sequentially, hydrogenation canprecede oxidation or oxidation can precede hydrogenation. Suitablehydrogenating agents for use in the present reaction include hydrogengas in combination with a metal catalyst, such as palladium (e.g.,palladium on carbon). Suitable conditions for carrying out suchreactions are described in House, Modern Synthetic Reactions, 2nd ed.,Menlo Park, Calif.: The Benjamin/Cummings Publishing Company, pp. 1-34(1972) (“House”), which is hereby incorporated by reference. Suitableoxidizing agents for use in the present reaction include those which aregenerally known to dehydrogenate 1,4-cyclohexadienyl moieties to phenylmoieties, such as 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (“DDQ”) andtetrachlorobenzoquinone (a.k.a., chloranil). Other suitable oxidizingagents and suitable conditions for carrying out such reactions aredescribed, for example, at pages 33-44 of House, which is herebyincorporated by reference.

[0147] The above-described method is useful for making compounds havingFormula XLVI in which Y is an alkoxycarbonyl group (e.g., in which Y hasthe formula —COOR¹² and R¹² is an alkyl group) and/or in which R¹ andR³, together with the atoms to which they are bonded, form an aromaticring, such as a 3,4-dichlorophenyl ring. In the latter case, thecompound of Formula XLVI has the formula (“Formula XLVII”):

[0148] Furthermore, by using a cyclohexadiene having Formula XLIV (e.g.,a cyclohexadiene having Formula XLV), substantially enantiomericallypure compounds of Formula XLVI, such as those having the formula(“Formula XLVIII”):

[0149] for example, those having the formula (“Formula XLIX”):

[0150] can be prepared.

[0151] The compound having Formula XLVI can be used to make a compoundhaving the formula (“Formula L”):

[0152] where R¹, R², R³, R⁵⁴, R⁵⁶, and R⁵⁸ are defined as they were withregard to Formula XLVI. R⁶² represents an alkyl moiety, examples ofwhich include methyl, ethyl, or propyl groups, which can optionally besubstituted with, for example, aryl groups (optionally containing aheteroatom) (e.g., pyrid-4-ylmethyl) or amino groups (which are meant toinclude amines that are unsubstituted or mono- or di-substituted with,for example, alkyl or aryl groups) (e.g.,2-(N,N-diisopropylamino)ethyl). Alternatively, R⁶⁵ and R⁶² togetherrepresent the atoms necessary to complete a 5-12 membered ring, in whichcase the compound produced has the formula (“Formula LI”):

[0153] In this formula, Z⁶ represents, for example, an alkylene group(e.g., a group having the formula —CH₂CH₂—, —CH₂CH₂CH₂—,—CH(NH₂)CH₂CH₂—, —CH₂CH₂CH(NH₂)—, —CH₂NRCH₂—, —CH₂CH(C₆H₅)CH₂—, etc.).Specific compounds of Formula L which can be made using this methodinclude 1,1-diarylalkanes, such as the pharmaceuticals tolterodine andCDP-840, which respectively have the formulae:

[0154] as well as nominfensine and sertraline, which respectively havethe formulae:

[0155] Conditions effective for achieving the conversion of compounds ofFormula XLVI to compounds of Formula L depend on the nature of thedesired substituents at R⁶² and R⁶⁵. Illustratively, in the case whereR⁶² and R⁶⁵ are discreet moieties (i.e., in the case where R⁶² and R⁶⁵do not combine to form a ring structure), R⁵⁹ can be chosen so that nofurther chemistry is required at that position to obtain the desired R⁶⁵substituent, and the —CH₂CH₂Y moiety can be converted to the desired R⁶²substituent using conventional methods. In the case where R⁶² and R⁶⁵combine to form a ring, conventional cyclization chemistry can beemployed. For example, in the case where R⁵⁹ is H and R⁶² and R⁶⁵together represent a —CH₂CH₂CH₂— moiety, cyclization can be carried outusing, for example, a Friedel—Crafts acylation catalyst.

[0156] The above method for making compounds having Formula LI isillustrated by the following procedure for making sertraline orsertraline congeners having the formula (“Formula LII”):

[0157] In Formula LII, R¹, R², R³, R⁵⁴, R⁵⁵, R⁵⁶ and R⁵⁸ defined as theywere above with regard to compounds of Formula XLVI. R⁶⁰ is H. R⁶¹ canrepresent a substituted or unsubstituted amine, such as an amine havingthe formula —NR⁶³R⁶⁴, where each of R⁶³ and R⁶⁴ is independentlyselected from hydrogen, an alkyl group, and an aryl group.Illustratively, R⁶¹ can be a dialkyl amino group (e.g., N(CH₃)₂), amonoalkylamino group (e.g., —NHCH₂CH₃), or a monoarylamino group (e.g.,—NH(C₆H₅)), or R⁶¹ can represent a cyclic amine moiety, such as apiperidinyl group or a morpholino group. Alternately, R⁶⁰ and R⁶¹,together with the carbon atom to which they are bonded, can represent acarbonyl (i.e., a C═O) moiety.

[0158] The method includes providing a cyclohexadiene derivative havingFormula XXXIX in which Y is an electron withdrawing group, such as anyone of the electron-withdrawing groups described above, and R⁵⁷ and R⁵⁹are H. Cyclohexadiene derivatives which can be used in this reaction arethose described above. Once the cyclohexadiene derivative is provided,it is converted with hydrogenating, oxidizing, and cyclizing agentsunder conditions effective to form the compound of Formula LII. Thehydrogenation and oxidation reactions can be carried out simultaneouslyor sequentially, and, when carried out sequentially, hydrogenation canprecede oxidation or oxidation can precede hydrogenation.Illustratively, both hydrogenation and oxidation can precedecyclization, as in the case where the cyclohexadiene derivative isconverted with a hydrogenating agent and an oxidizing agent into acompound of Formula XLVI and where the phenyl derivative is thenconverted with a cyclizing agent under conditions effective to producethe compound.

[0159] Suitable hydrogenating and oxidizing agents and methods for theiruse are described above. Cyclizing agents suitable for use in thepractice of the present invention include acylation catalysts, such asFriedel Crafts acylation catalysts, examples of which include ClSO₃H,AlCl₃, and other Lewis acids. In the case where Y is an alkoxycarbonylgroup, the alkoxy group can be converted to a hydroxy group, prior totreatment with the Friedel Crafts acylation catalyst. This can be doneusing strong acid, e.g., 6 N HCl, or by any other suitable method. Theimmediate product of such a cyclization is a tetralone having theformula (“Formula LIII”):

[0160] which can be readily converted to compounds having Formula LII bymethods known to those skilled in the art, such as the reductiveamination method set forth in Corey et al., Tetrahedron Lett.,35:5373-5376 (1994), which is hereby incorporated by reference.

[0161] The above-described method is useful for making compounds havingFormula LII in which Y is an alkoxycarbonyl group (e.g., in which Y hasthe formula —COOR¹² and R¹² is an alkyl group) and/or in which R¹ andR³, together with the atoms to which they are bonded, form an aromaticring, such as a 3,4-dichlorophenyl ring, in which case the compound ofFormula LII can have the formula (“Formula LIV”):

[0162] Furthermore, by using a cyclohexadiene having Formula XL (e.g., acyclohexadiene having Formula XLV), substantially enantiomerically purecompounds of Formula LII, such as those having the formula (“FormulaLV”):

[0163] for example, those having the formula (“Formula LVI”):

[0164] can be prepared.

[0165] Further details regarding these reactions as well as furtherdiscussion regarding the synthesis of diarylacetates,4,4-diarylbutanoates, and other ω,ω-diarylalkanoates are set forth, forexample, in Davies et al., “Catalytic Asymmetric Synthesis ofDiarylacetates and 4,4-Diarylbutanoates. A Formal Asymmetric Synthesisof (+)-Sertraline,” Organic Letters, 1(2):233-236 (1999), which ishereby incorporated by reference.

[0166] Other reactions that can benefit by the practice of the methodsand use of the compositions of the present invention include thosedescribed in Davies et al., “Effect of Carbenoid Structure on theReactions of Rhodium—Stabilized Carbenoids with Cycloheptatriene,”Tetrahedron Letters, 41:2035-2038 (2000) and U.S. Pat. No. 5,175,311 toDoyle, which are hereby incorporated by reference.

[0167] Further details with regard to methods for using the compositionsof the present invention are set forth below in the section labeled“Examples”.

[0168] Once the catalytic reaction is completed (or, if desired, evenbefore completion of the reaction), the rhodium catalyst composition ofthe present invention can be separated from the reaction mixture, forexample, for reuse in a subsequent reaction. The exact method foreffecting such separation depends, in part, on the nature of the solidsupport used in the rhodium catalyst composition. For example, where thesolid support used in the rhodium catalyst composition is in the form ofbeads (or where the solid support is coated onto an inert beadsubstrate, e.g., glass or stainless steel beads), separation canconveniently be achieved by filtration, centrifugation, etc.). Othermethods for separating catalysts from reaction mixtures include thosewell known in the art of heterogeneous catalysis.

[0169] The present invention is further illustrated by the followingnon-limiting examples.

EXAMPLES Example 1 Preparation and Catalytic Properties of DirhodiumCatalyst Compositions

[0170] In order to immobilize chiral dirhodium tetracarboxylatecatalysts 1-3 without resorting to ligand modification, we decided tostudy the use of polymer-supported pyridines.

[0171] In this regard, we hypothesized that such polymer-supportedpyridines may interact with the dirhodium tetracarboxylate catalysts asshown in Scheme 1. More particularly, we hypothesized that the dirhodiumcomplex could coordinate to the polymer-supported pyridine to form 4,and the other rhodium center in 4 could react with diazo compounds toform the corresponding carbenoid 5.

[0172] ArgoPore® resin, modified with a pyridinyl group attached to thepolymer backbone via a benzyl spacer, was used as the solid support.Referring to Scheme 2, the hydroxy group in ArgoPore®-Wang resin(hydroxyl loading=0.65 mmol/g) (available from Argonaut Technologies)was converted to the bromide 6 with PPh₃ and CBr₄, and 6 was reactedwith the sodium alkoxide of 4-pyridinylmethanol to give 7. To immobilizeRh₂(S-TBSP)₄, the pyridine resin 7 was gently stirred with Rh₂(S-TBSP) 4in dichloromethane. The color of the resin changed from pale brown topurple indicating coordination of the pyridine to the rhodium metal.After filtration of the solvent, the resin was washed withdichloromethane (9 times), and was dried under vacuum. In a similar way,Rh₂(S-biTISP)₂ was immobilized on the resin 7. The loading of therhodium complex was estimated by the increase of the weight of theresin. The loading of Rh₂(S-TBSP)₄ in 7 was 0.18 mmol/g, and that ofRh₂(S-biTISP)₂ was 0.17 mmol/g.

[0173] A standard cyclopropanation was used to evaluate the catalyticactivity of ‘7-Rh₂(S-TBSP)₄’ and ‘7-Rh₂(S-biTISP)₂’. Dropwise additionof methyl phenyldiazoacetate to a solution of styrene (2 equiv) with theresin (0.5 mol %) in toluene as solvent resulted in efficientcyclopropanation. The rate of the reaction was found to depend on therate of stirring, and so all the reactions were run with approximatelythe same stirring rate. The end-point of the reaction was judged by thecessation of the evolution of nitrogen gas. The resin was rinsed withtoluene (5 times) and dried before re-use in the next cycle.

[0174] As shown in Table 1, the cyclopropanation with ‘7-Rh₂(S-TBSP)₄’gave the cyclopropanation product in good yield (92-89%) anddiastereoselectivity (>94% de); however, the enantiomeric excess (ee)dropped steadily from 82% to 70% over 4 cycles. TABLE 1

7-Rh₂(S-TBSP)₄ 7-Rh₂(S-biTISP)₂ time yield ee time yield ee Cycle (min)(%) (%) Cycle (min) (%) (%) 1 10 92 82 1 18 91 85 2 17 91 78 2 23 91 863 14 89 73 3 26 90 87 4 14 89 70 4 36 90 87 10 60 87 88 15 92 89 88

[0175] We believe that this indicates that the prolinate catalysts areundergoing slow degradation under the reaction conditions. This wouldalso explain why there is a drop in enantioselectivity using recycledcatalyst. In contrast, ‘7-Rh₂(S-biTISP)₂’ appears to be a very robustcatalyst as the yield (87-91%) and the enantioselectivity (85-88% ee)remain steady over 15 cycles. The only change is in the reaction time,which increases by a factor of six over the 15 cycles. ‘7-Rh₂(S-TBSP)₄’gave the (S,S)-cyclopropane, and ‘7-Rh₂(S-biTISP)₂’ gave the(R,R)-cyclopropane. In order to further evaluate the catalytic activityof ‘7-Rh₂(S-biTISP)₂’, the reactions of several diazo compounds usinglower equivalents of the catalyst were examined. As shown in Table 2,the reaction with methyl phenyldiazoacetate (entry 1) was similarlyachieved (88% yield, 88% ee) with 0.04 mol % of ‘7-Rh₂(S-biTISP)₂’, butthe reaction took 3 h to reach completion. With the otheraryldiazoacetates (entries 2-5), 0.1 mol % of the catalyst was used andhigh yields and enantioselectivities of the products were consistentlyobtained (entries 2-5). The styryldiazoacetate (entry 6) was alsoeffective, but the reaction was slower than that of thearyldiazoacetates. TABLE 2

time catalyst yield ee entry R (min) (mol %) (%) (%) 1

180 0.04 88 88 2

120 0.1 89 74 3

60 0.1 90 80 4

60 0.1 89 83 5

60 0.1 87 90 6

420 0.1 82 68

[0176] To investigate the whether the immobilized dirhodium catalystcompositions can be used to prepare compound libraries, a series ofcyclopropanations was carried out using recycled catalyst. The resultsare summarized in Table 3. The yields and the ee's are comparable tothose obtained with the ‘fresh’ catalyst, the latter being shown inTable 2. With 0.5 mol % of the catalyst, all the reactions werecompleted within 30 min. Furthermore, from the ¹H NMR spectra of thecrude mixture, there was no cross-contamination between successivecyclopropanations. This would indicate that the product is efficientlywashed from the polymer support between cycles even though the catalystis retained. TABLE 3

reaction yield ee cycle R time (min) (%) (%) 1

16 82 71 2

30 86 76 3

5 84 80 4

30 85 80 5

30 94 90

[0177] In some regards, the success of this chemistry is surprisingbecause donor groups such as pyridine tend to deactivate dirhodiumtetracarboxylates. Therefore, control experiments were carried out tofurther understand the unexpectedly high efficiency of the‘7-Rh₂(S-biTISP)₂’ catalyst composition.

[0178] To study the effect of pyridine, both Rh₂(S-TBSP)₄ andRh₂(S-biTISP)₂ were mixed with 1.5 equiv of 4-alkylpyridine 8, as shownin Scheme 3. SCHEME 3

catalyst time, min yield, % ee, % Rh₂(S-TBSP)₄/8  10 43 81Rh₂(S-biTISP)₂/8 720 18 88

[0179] The cyclopropanation of styrene with phenyldiazoacetate usingthese catalysts was conducted in toluene. With Rh₂(S-TBSP)₄ coordinatedto 8, the reaction was complete in 10 min but the yield was only 43%.Rh₂(S-biTISP)₂ coordinated to 8 showed very little catalytic activity.Even after 12 h, the yield of cyclopropanation was only 18%, and manyunidentified side products were observed by ¹H NMR of the crude mixture.In both cases, however, enantioselectivity remained high. These resultssuggest that coordination of pyridine to Rh₂(S-biTISP)₂ significantlydecreases its catalytic activity and that, in the ‘7-Rh₂(S-biTISP)₂’catalyst, the ‘active’ catalyst is not Rh₂(S-biTISP)₂ coordinated to thepyridine.

[0180] In order to further determine the importance of the pyridinegroup, a second control experiment was undertaken, as shown in Scheme 4.The analogous phenyl-substituted resin 9 was prepared, and it was foundthat it also could immobilize Rh₂(S-TBSP)₄ and Rh₂(S-biTISP)₂. The resin9 was treated with either Rh₂(S-TBSP)₄ or Rh₂(S-biTISP)₂ in toluene, andthe resin was then washed with toluene (5 times). The resultinggreen-colored resins contained 0.11 mmol/g of Rh₂(S-TBSP)₄, and 0.07mmol/g of Rh₂(S-biTISP)₂, respectively.

[0181] With the phenyl-substituted resin catalysts, five cycles ofcyclopropanation of styrene with methyl phenyldiazoacetate were tried.As shown in Table 4, the reaction with the phenyl resin ‘9-Rh₂(S-TBSP)₄’gave the cyclopropanation product in good yields (90-92%); however, theenantioselectivity dropped slightly from 85% to 81% ee. The reactionwith the phenyl-resin ‘9-Rh₂(S-biTISP)₂’ maintained the same level ofenantioselectivity over four cycles; however, longer reaction times wererequired to complete the reaction. TABLE 4

9-Rh₂(S-TBSP)₄ 9-Rh₂(S-biTISP)₂ time yield ee time yield ee Cycle (min)(%) (%) Cycle (min) (%) (%) 1 21 92 85 1 24 85 82 3 19 91 83 3 37 84 845 15 90 81 5 57 83 84

[0182] These control experiments suggest that, perhaps, the actualcatalyst in the pyridine-resin 7 is not the pyridine coordinateddirhodium complex. At present, it is not clear whether catalystimmobilization in the nitrogen-containing solid support/catalystcompositions is due to a microencapsulation effect (as is likely to bethe case where the phenyl-containing solid support/catalyst is employed)or whether catalyst immobilization in the nitrogen-containing solidsupport/catalyst compositions is due to a coordination of the nitrogenatom to a rhodium atom. Irrespective of the mechanism of binding, theresults demonstrate that dirhodium catalysts can be immobilized orotherwise bound to solid supports, that the catalyst/solid supportcompositions are active as catalysts, and that the catalyst/solidsupport compositions can be recycled 15 times, while the products arereadily removed by solvent washing.

Example 2 Preparation of 4-(Bromomethyl)phenoxymethyl-Polystyrene (6)

[0183] To a suspension of Argopore-Wang Resin (loading 0.65 mmol/g, 1.04g, 0.676 mmol) in dichloromethane (“DCM”) (7 mL) was added CBr₄ (0.607g, 1.83 mmol). After cooling to 0° C. (ice-water bath), PPh₃ (0.385 g,1.46 mmol) in DCM (1 mL) was added. After 2.5 h, the cooling bath wasremoved, and the mixture was stirred for 3 h at 23° C. The solvent wasremoved by filtration. The resin was washed with DCM (8×25 mL), and therecovered solid was air dried under vacuum to give 0.95 g of resin.

Example 3 Preparation of4-[4-(Pyridinyl)methoxymethyl]phenoxymethyl-Polystyrene (7)

[0184] To NaH (60% in mineral oil, 66 mg, 1.64 mmol) was added asolution of 4-pyridinecarbinol (0.250 g, 2.29 mmol) in tetrahydrofuran(“THF”) (1 mL) in one portion at 0° C. After 30 min, the cooling bathwas removed, and the mixture was stirred at 23° C. for 7 h. Bu₄NI (0.61g, 1.65 mmol) in dimethylformamide (“DMF”) (5 mL) was added, and, 15 minlater, Bromomethyl Resin 6 (0.477 g) was added in one portion. Themixture was gently stirred for 64 h, and the solvent was removed byfiltration. The resin was washed with THF (3×), DMF-H₂O (2:1, 3×), DMF(3×), THF (3×), and DCM (3×), and was dried under vacuum to give lightbrown beads (0.455 g).

Example 4 Preparation of (Benzyloxymethyl)phenoxymethyl-Polystyrene (9)

[0185] To a suspension of NaH (60% in mineral oil, 83 mg, 2.1 mmol) inTHF (8 mL) was added benzyl alcohol (0.46 g, 4.3 mmol) at 23° C. After 1d, this solution was added to a suspension of Bromomethyl Resin 6 (0.504g) with Bu₄NI (38 mg, 0.10 mmol) in DMF (8 mL) at 23° C. The mixture wasstirred gently for 1.5 d, and the solvent was removed by filtration. Theresin was washed with THF (2×), DMF-H₂O (1:1, 3×), DMF (3×), THF (3×),H₂O (3×), DMF (3×), and THF (3×). The resin was dried under vacuum togive light brown beads (0.475 g).

Example 5 Immobilization of Rh₂(S-TBSP)₄ in Pyridine-Resin 7

[0186] To a mixture of Pyridine—Resin 7 (48.6 mg) and Rh₂(S-TBSP)₄ (38.8mg, 0.268 mmol) was added DCM (5.5 mL) at 23° C. The mixture was gentlystirred for 9 min; then Pyridine—Resin 7 (9.4 mg) was added again; andthe resulting mixture was further stirred gently for 3 h. Most of thesolvent was removed by a pipet, and DCM (5 mL) was added. The mixturewas gently stirred for 5 min, and then most of the DCM was removed by apipet. This procedure was repeated two more times, and then the resinwas transferred to a funnel and washed with DCM (6×). The resin wasdried under vacuum to give purple beads (0.105 9).

Example 6 Immobilization of Rh₂(S-biTISP)₂ in Pyridine—Resin 7

[0187] To a solution of Rh₂(S-biTISP)₂ (57 mg, 0.030 mmol) in toluene (4mL) was added Pyridine—Resin 7 (76.3 mg) in one portion. The mixture wasswirled on a shaker (400-500 rpm) at 23° C. for 7 h, and then thesolvent was removed by filtration. The resin was washed with toluene(9×5 mL) and was dried under vacuum to give purple beads (0.118 g,loading of Rh₂(S-biTISP)₂=0.17 mmol/g)

Example 7 Immobilization of Rh₂(S-TBSP)₄ in Phenyl-Resin 9

[0188] To a solution of Rh₂(S-TBSP)₄ (0.186 g, 0.128 mmol) in toluene (5mL) was added Phenyl-Resin 9 (0.114 g). The mixture was swirled on ashaker (400-500 rpm) at 23° C. for 16 h. The solvent was removed byfiltration. The resin was washed with toluene (10×5 mL) and was driedunder vacuum to give light green beads (0.136 g).

Example 8 Immobilization of Rh₂(S-biTISP)₂ in Phenyl-Resin 9

[0189] To a solution of Rh₂(S-biTISP)₂ (8.5 mg, 0.0045 mmol) in toluene(1 mL) was added Phenyl-Resin 9 (38.8 mg) in one portion, and thentoluene (1 mL) was added. The mixture was swirled on a shaker (400-500rpm) for 6 d. The solvent was removed by filtration. The resin waswashed with toluene (5×) and was dried under vacuum to give green beads(44.7 mg).

Example 9 Immobilization of Rh₂(S-TBSP)₄ in Polystyrene-DMAP Resin

[0190] Rh₂(S-TBSP)₄ was immobilized in commercial polystyrene-DMAP resin(“PS-DMAP”, Argonaut Technologies, Inc.) in accordance with thefollowing Scheme 5.

[0191] The polystyrene resin in PS-DMAP was cross-linked with 4%divinylbenzene, and the loading of the pyridyl group was 1.42 mmol/g.The product was obtained as brown beads and had a Rh₂(S-TBSP)₄ loadingof 0.098 mmol/g.

Example 10 General Procedure for Cyclopropanation Reactions

[0192] A Buchner funnel with a fritted disc (fine porosity) was used asa reaction vessel. To facilitate efficient stirring of the reactionmixture with a magnetic stirring bar, the stem of the funnel was cut toabout ½ inch. A positive pressure of argon gas was introduced throughthe stem of the funnel to prevent the reaction mixture from drippingthrough the disc. Rubber septa were used to seal the top and bottom ofthe funnel, and a needle was introduced through the top septum andconnected via tubing to a bubbler to monitor evolution of gas from thereaction mixture.

[0193] Rh₂(S-biTISP)₂ immobilized Pyridine—Resin 7 (loading 0.17 mmol/g,14.2 g, 0.0024 mmol) was put in the reaction vessel and argon gas wasgently purged from the bottom for 10 min. Styrene (0.118 g, 1.13 mmol)in toluene (1 mL) was added. After 1 min, methyl phenyldiazoacetate(91.0 mg, 0.517 mmol) in toluene (1 mL) was added dropwise over 5 min at23° C. with efficient stirring. After 13 min, the solvent was drained,and the resin was washed with toluene (5×5 mL). All of the filtrateswere combined, and the cyclopropanation product was purified bypreparative TLC (using hexanes/diethyl ether (2:1) as the eluent) togive white solid (0.470 mg, 91% yield). The enantiomeric excess wasmeasured to be 85% by chiral HPLC with a (R,R)-Whelk-O column (using 2%isopropanol in hexanes as the eluent). The resin in the reaction vesselwas dried under vacuum and was reused in the next cycle.

[0194] Although the invention has been described in detail for thepurpose of illustration, it is understood that such detail is solely forthat purpose, and variations can be made therein by those skilled in theart without departing from the spirit and scope of the invention whichis defined by the claims that are set forth below.

What is claimed is:
 1. A dirhodium catalyst composition comprising: adirhodium catalyst which comprises a Rh—Rh moiety and four bridgingligand moieties; and a solid support, wherein said dirhodium catalystand said solid support are bound together and wherein said dirhodiumcatalyst and said solid support are not covalently bound together viaone or more of said bridging ligand moieties.
 2. A composition accordingto claim 1, wherein each of the four ligand moieties are independentlyselected from carboxylate moieties and amide moieties.
 3. A compositionaccording to claim 1, wherein said dirhodium catalyst is a dirhodiumtetracarboxylate catalyst.
 4. A composition according to claim 1,wherein said dirhodium catalyst is a dirhodium tetracarboxamidatecatalyst.
 5. A composition according to claim 1, wherein said solidsupport is a macroporous solid support.
 6. A composition according toclaim 1, wherein said solid support is a cross-linked polystyrene resin.7. A composition according to claim 1, wherein said solid support is amacroporous cross-linked polystyrene resin.
 8. A composition accordingto claim 1, wherein said solid support is a cross-linked polystyreneresin and wherein the cross-linked polystyrene resin is more highlycross-linked than a 1% cross-linked polystyrene resin.
 9. A compositionaccording to claim 1, wherein said solid support is a cross-linkedpolystyrene resin comprising pendant groups having the formula:

wherein W represents H, halogen, a hydroxy group, a thiol group, analkoxy group, an alkylthio group, an aryl thio group, or combinationsthereof.
 10. A composition according to claim 9, wherein W represents ahydroxyl group, a halogen, or an alkoxy group.
 11. A compositionaccording to claim 9, wherein W represents an alkoxy group.
 12. Acomposition according to claim 9, wherein W represents a —OW′ group andwherein W′ is an aryl group.
 13. A composition according to claim 9,wherein W represents a —OW′ group and wherein W′ is a substituted orunsubstituted phenyl group or a substituted or unsubstituted pyridylgroup.
 14. A composition according to claim 9, wherein W represents a—OW′ group and wherein W′ is a phenyl group or 4-pyridyl group.
 15. Acomposition according to claim 9, wherein W represents a —OW′ group andwherein W′ is nitrogen-containing heterocycle.
 16. A compositionaccording to claim 15, wherein the nitrogen-containing heterocycle is apyridyl group, a quinolinyl group, an isoquinolinyl group, an imidazolylgroup, or a benzimidazolyl group.
 17. A composition according to claim1, wherein said solid support is a cross-linked polystyrene resincomprising pendant groups having the formula:

wherein W represents H, halogen, a hydroxy group, a thiol group, analkoxy group, an alkylthio group, an aryl thio group, or combinationsthereof.
 18. A composition according to claim 1, wherein said solidsupport comprises a nitrogen-containing heterocyclic pendant group. 19.A composition according to claim 18, wherein the nitrogen-containingheterocyclic pendant group is a pyridyl group, a quinolinyl group, anisoquinolinyl group, an imidazolyl group, or a benzimidazolyl group. 20.A composition according to claim 1, wherein said solid support comprisesa nitrogen-containing heterocyclic pendant group and wherein saiddirhodium catalyst and said solid support are bound together via a bondbetween at least one of the rhodiums' axial positions and theheterocyclic pendant group's nitrogen.
 21. A composition according toclaim 1, wherein said solid support comprises a pendant substituted orunsubstituted phenyl group.
 22. A composition according to claim 1,wherein said dirhodium catalyst is a chiral dirhodium catalyst.
 23. Acomposition according to claim 1, wherein said dirhodium catalyst is achiral dirhodium tetracarboxylate catalyst.
 24. A composition accordingto claim 1, wherein said dirhodium catalyst is a chiral dirhodiumtetracarboxamidate catalyst.
 25. A composition according to claim 1,wherein said dirhodium catalyst has the formula:

wherein each of M¹ and M² is Rh; Z⁴ represents the atoms necessary tocomplete a 3-12 membered heterocyclic ring; and Q³ is an electronwithdrawing group.
 26. A composition according to claim 25, wherein Z⁴has the formula —CH₂CH₂CH₂—.
 27. A composition according to claim 25,wherein said dirhodium tetracarboxylate catalyst has one of thefollowing formulae:


28. A composition according to claim 25, wherein said dirhodiumtetracarboxylate catalyst has D₂ symmetry.
 29. A composition accordingto claim 1, wherein said dirhodium catalyst is a dirhodiumtetracarboxylate catalyst having the formula:

wherein each of M¹ and M² is Rh; Z² and Z³, independently, are the atomsnecessary to complete a 3-12 membered heterocyclic ring; Z¹ is analkylene or arylene group; Q¹ and Q² are the same or different and areelectron withdrawing groups; L¹ and L³, taken together, represent—O—CR³—O—; L² and L⁴, taken together, represent —O—CR¹⁴—O—; and R¹³ andR¹⁴ are the same or different and are selected from the group consistingof alkyl groups and aryl groups or R¹³ and R¹⁴ represent alkylene orarylene groups that are directly or indirectly bonded to one another.30. A composition according to claim 29, wherein said dirhodiumtetracarboxylate catalyst has the formula:


31. A composition according to claim 29, wherein Z² and Z³ each have theformula —CH₂CH₂—.
 32. A composition according to claim 29, wherein Z¹ isa 1,3-phenylene moiety.
 33. A composition according to claim 29, whereinsaid dirhodium tetracarboxylate catalyst has one of the followingformulae:


34. A composition according to claim 29, wherein said dirhodiumtetracarboxylate catalyst has one of the following formulae:

wherein R¹ and R² are the same or different and are alkyl or arylgroups.
 35. A composition according to claim 1, wherein said dirhodiumcatalyst has the following formula:

wherein each of M¹ and M² is Rh; W³ represents an alkyl group, an arylgroup, an alkoxy group, or an amine group; W⁴ represents an alkyl groupor an aryl group; or W³ and W⁴, taken together, represent the atomsnecessary to complete a 3-12 membered heterocyclic ring.
 36. A dirhodiumcatalyst composition comprising: a dirhodium tetracarboxylate catalyst;and a solid support, wherein said dirhodium tetracarboxylate catalystand said solid support are bound together.
 37. A dirhodium catalystcomposition according to claim 36, wherein said dirhodiumtetracarboxylate catalyst has the formula:

wherein each of M¹ and M² is Rh; Z⁴ represents the atoms necessary tocomplete a 3-12 membered heterocyclic ring; and Q³ is an electronwithdrawing group.
 38. A dirhodium catalyst composition according toclaim 36, wherein said dirhodium tetracarboxylate catalyst has theformula:

wherein each of M¹ and M² is Rh; Z² and Z³, independently, are the atomsnecessary to complete a 3-12 membered heterocyclic ring; Z¹ is analkylene or arylene group; Q¹ and Q² are the same or different and areelectron withdrawing groups; L¹ and L³, taken together, represent—O—CR¹³—O—; L² and L⁴, taken together, represent —O—CR¹⁴—O—; and R¹³ andR¹⁴ are the same or different and are selected from the group consistingof alkyl groups and aryl groups or R¹³ and R¹⁴ represent alkylene orarylene groups that are directly or indirectly bonded to one another.39. A dirhodium catalyst composition according to claim 36, wherein saiddirhodium tetracarboxylate catalyst is a chiral dirhodiumtetracarboxylate catalyst.
 40. A dirhodium catalyst compositioncomprising: a dirhodium catalyst comprising a Rh—Rh moiety; and a solidsupport, wherein said dirhodium catalyst and said solid support arebound together via at least one of the rhodiums' axial positions.
 41. Acomposition according to claim 40, wherein the solid support comprises anitrogen-containing heterocyclic pendant group and wherein saiddirhodium catalyst and said solid support are bound together via a bondbetween at least one of the rhodiums' axial positions and theheterocyclic pendant group's nitrogen.
 42. A composition according toclaim 41, wherein the nitrogen-containing heterocyclic pendant group isa pyridyl group, a quinolinyl group, an isoquinolinyl group, animidazolyl group, or a benzimidazolyl group.
 43. A method for making adirhodium catalyst composition according to claim 1, said methodcomprising: providing a dirhodium catalyst which comprises a Rh—Rhmoiety and four bridging ligand moieties; and contacting the dirhodiumcatalyst with a solid support under conditions effective to bind thedirhodium catalyst and the solid support together and to produce thedirhodium catalyst composition.
 44. A method according to claim 43,wherein each of the four bridging ligand moieties are independentlyselected from carboxylate moieties and amide moieties.
 45. A methodaccording to claim 43, wherein the dirhodium catalyst is a dirhodiumtetracarboxylate catalyst.
 46. A method according to claim 43, whereinthe dirhodium catalyst is a dirhodium tetracarboxamidate catalyst.
 47. Amethod according to claim 43, wherein the dirhodium catalyst is a chiraldirhodium catalyst.
 48. A method according to claim 43, wherein thedirhodium catalyst has the formula:

wherein each of M¹ and M² is Rh; Z⁴ represents the atoms necessary tocomplete a 3-12 membered heterocyclic ring; and Q³ is an electronwithdrawing group.
 49. A method according to claim 48, wherein Z⁴ hasthe formula —CH₂CH₂CH₂—.
 50. A method according to claim 48, wherein thedirhodium tetracarboxylate catalyst has one of the following formulae:


51. A method according to claim 48, wherein the dirhodiumtetracarboxylate catalyst has D₂ symmetry.
 52. A method according toclaim 43, wherein the dirhodium tetracarboxylate catalyst has theformula:

wherein each of M¹ and M² is Rh; Z² and Z³, independently, are the atomsnecessary to complete a 3-12 membered heterocyclic ring; Z¹ is analkylene or arylene group; Q¹ and Q² are the same or different and areelectron withdrawing groups; L¹ and L³, taken together, represent—O—CR¹³—O—; L² and L⁴, taken together, represent —O—CR¹⁴—O—; and R¹³ andR¹⁴ are the same or different and are selected from the group consistingof alkyl groups and aryl groups or R¹³ and R¹⁴ represent alkylene orarylene groups that are directly or indirectly bonded to one another.53. A method according to claim 52, wherein the dirhodiumtetracarboxylate catalyst has the formula:


54. A method according to claim 52, wherein Z² and Z³ each have theformula —CH₂CH₂—.
 55. A method according to claim 52, wherein Z¹ is a1,3-phenylene moiety.
 56. A method according to claim 52, wherein thedirhodium tetracarboxylate catalyst has one of the following formulae:


57. A method according to claim 52, wherein the dirhodiumtetracarboxylate catalyst has one of the following formulae:

wherein R¹ and R² are the same or different and are alkyl or arylgroups.
 58. A method according to claim 43, wherein the solid supportcomprises a nitrogen-containing heterocyclic pendant group.
 59. A methodaccording to claim 58, wherein the nitrogen containing heterocyclicpendant group is a pyridyl group, a quinolinyl group, an isoquinolinylgroup, an imidazolyl group, or a benzimidazolyl group.
 60. A methodaccording to claim 43, wherein the solid support comprises anitrogen-containing heterocyclic pendant group and wherein the dirhodiumcatalyst and the solid support are bound together via a bond between atleast one of the rhodiums' axial positions and the heterocyclic pendantgroup's nitrogen.
 61. A method according to claim 43, wherein the solidsupport comprises a pendant substituted or unsubstituted phenyl group.62. A method for making a dirhodium catalyst composition according toclaim 36, said method comprising: providing a dirhodium tetracarboxylatecatalyst; and contacting the dirhodium tetracarboxylate catalyst with asolid support under conditions effective to bind the dirhodiumtetracarboxylate catalyst and the solid support together and to producethe dirhodium catalyst composition.
 63. A method according to claim 62,wherein the dirhodium tetracarboxylate catalyst has the formula:

wherein each of M¹ and M² is Rh; Z⁴ represents the atoms necessary tocomplete a 3-12 membered heterocyclic ring; and Q³ is an electronwithdrawing group.
 64. A method according to claim 62, wherein thedirhodium tetracarboxylate catalyst has the formula:

wherein each of M¹ and M² is Rh; Z² and Z³, independently, are the atomsnecessary to complete a 3-12 membered heterocyclic ring; Z¹ is analkylene or arylene group; Q¹ and Q² are the same or different and areelectron withdrawing groups; L¹ and L³, taken together, represent—O—CR¹³—O—; L² and L⁴, taken together, represent —O—CR¹⁴—O—; and R¹³ andR¹⁴ are the same or different and are selected from the group consistingof alkyl groups and aryl groups or R¹³ and R¹⁴ represent alkylene orarylene groups that are directly or indirectly bonded to one another.65. A method according to claim 62, wherein said dirhodiumtetracarboxylate catalyst is a chiral dirhodium tetracarboxylatecatalyst.
 66. A method for making a dirhodium catalyst compositionaccording to claim 40, said method comprising: providing a dirhodiumcatalyst comprising a Rh—Rh moiety; and contacting the dirhodiumcatalyst with a solid support under conditions effective to bind thedirhodium catalyst and the solid support together via at least one ofthe rhodiums' axial positions and to produce the dirhodium catalystcomposition.
 67. A method according to claim 66, wherein the solidsupport comprises a nitrogen-containing heterocyclic pendant group andwherein the dirhodium catalyst and the solid support are bound togethervia a bond between at least one of the rhodiums' axial positions and theheterocyclic pendant group's nitrogen.
 68. A composition according toclaim 67, wherein the nitrogen-containing heterocyclic pendant group isa pyridyl group, a quinolinyl group, an isoquinolinyl group, animidazolyl group, or a benzimidazolyl group.
 69. A method of producing acompound having the following formula (CI):

where R¹, R², and R³ are independently selected from H, alkyl, aryl, orvinyl or where R¹ and R³, together with the atoms to which they arebonded, form a 5-12 membered ring; Y is an electron withdrawing group; Xis CH₂, O, or NR¹¹; R¹¹ is H, an alkyl group, an aryl group, an acylgroup, an alkoxycarbonyl group, or a silyl group having the formula—SiR³³R³⁴R³⁵; each of R³⁰ and R³¹ is independently selected from thegroup consisting of H, alkyl, aryl, and vinyl; R³² is an alkyl group, anaryl group, an acyl group, an alkoxycarbonyl group, or a silyl grouphaving the formula —SiR³⁶R³⁷R³⁸; or R³¹ and R³², together with the atomsto which they are bonded, form a 5-12 membered ring; R³³, R³⁴, R³⁵, R³⁶,R³⁷, and R³⁸ are independently selected from an alkyl group and an arylgroup; provided that when each of R³⁰ and R³¹ is H, X is not CH₂, saidmethod comprising: providing a diazo compound having the formula:

and converting the diazo compound with a compound having the followingformula (CII):

in the presence of a dirhodium catalyst composition according to claim 1under conditions effective to produce the compound, wherein X′ is CH₂,O, or NR^(11′) and R^(11′) is an alkyl group, an aryl group, an acylgroup, an alkoxycarbonyl group, or a silyl group.
 70. A method accordingto claim 69, wherein R¹ and R³, together with the atoms to which theyare bonded, form a phenyl ring.
 71. A method according to claim 69,wherein the compound of formula (CI) has the following formula (CIII):

wherein R¹, R², and R³ are independently selected from H, alkyl, aryl,or vinyl or where R¹ and R³, together with the atoms to which they arebonded, form a 5-12 membered ring; Y is an electron withdrawing group; Xis CH₂, O, or NR¹¹; R¹¹ is H, an alkyl group, an aryl group, an acylgroup, an alkoxycarbonyl group, or a silyl group having the formula—SiR³³R³⁴R³⁵; R³³, R³⁴, and R³⁵ are independently selected from an alkylgroup and an aryl group; and n is 3-10; and wherein the compound offormula (CII) is a cyclic compound having the formula:

wherein X′ is CH₂, O, or NR^(11′); R^(11′) is an alkyl group, an arylgroup, an acyl group, an alkoxycarbonyl group, or a silyl group havingthe formula —SiR³³R³⁴R³⁵; and R³³, R³⁴, and R³⁵ are independentlyselected from an alkyl group and an aryl group.
 72. A method accordingto claim 71, wherein X is NH, Y is CO₂R¹², R¹² is a methyl group, n is4, and R¹ and R³, together with the atoms to which they are bonded, forma phenyl ring.
 73. A method according to claim 71, wherein the compoundof formula (CIII) has the formula:

and wherein the dirhodium catalyst is a chiral dirhodium catalyst.
 74. Amethod according to claim 73, wherein X is NH, Y is CO₂R¹², R¹² is amethyl group, n is 4, and R¹ and R³, together with the atoms to whichthey are bonded, form a phenyl ring.
 75. A method according to claim 69,wherein X is NR¹¹ and R³¹ and R³², taken together with the atoms towhich they are bonded, form a ring having the formula:

wherein R⁴¹, R⁴², and R⁴³ are independently selected from H, alkyl,aryl, or vinyl or wherein R⁴¹ and R⁴³, together with the atoms to whichthey are bonded, form a 5-12 membered ring; Y′ is an electronwithdrawing group; and m is 2-9; and wherein the compound of formula(CII) is a cyclic amine having the formula:


76. A method according to claim 75, wherein the compound has theformula:


77. A method of catalyzing an aryldiazomethane or a vinyldiazomethaneinsertion reaction, said method comprising: providing a aryldiazomethaneor a vinyldiazomethane; providing a dirhodium catalyst compositionaccording to claim 1; and contacting the aryldiazomethane or thevinyldiazomethane with the dirhodium catalyst composition underconditions effective to catalyze the aryldiazomethane orvinyldiazomethane insertion reaction.
 78. A compound produced by amethod according to claim
 77. 79. A compound containing a C—H bond,wherein said C—H bond is produced using a method according to claim 77.80. A method of producing a compound having the following formula (CIV):

where R¹, R², and R³ are independently selected from H, alkyl, aryl, orvinyl or where R¹ and R³, together with the atoms to which they arebonded, form a 5-12 membered ring; where Y is an electron withdrawinggroup; where R¹³¹ is H and R¹³⁰ is an alkyl group, an aryl group, analkoxy group, an amine group, or a silyl group; or where R¹³⁰ and R¹³¹,together with the atom to which they are bonded, form a substituted orunsubstituted cyclopropane moiety; said method comprising: providing adiazo compound having the formula:

and converting the diazo compound to the compound of formula (CIV) inthe presence of a dirhodium catalyst composition according to claim 1and under conditions effective to produce the compound of formula (CIV).81. A method according to claim 80, wherein the compound of formula(CIV) has the following formula (CV):

where Y is an electron withdrawing group; and where each of R¹³², R¹³³,and R¹³⁴, independently, represents H, an alkyl group, an aryl group, asilyloxy group, an alkoxy group, a halogen, an amine group, or an alkylor aryl thiol group; or where R¹³² and R¹³³, together with the atoms towhich they are bonded, form a 4-12 membered ring; or where R¹³³ andR¹³⁴, together with the atom to which they are bonded, form a 3-12membered ring; and wherein said converting is carried out using acompound having the following formula (CVI):


82. A method for preparing a cyclopentene, said method comprising:providing a compound of formula (CV) in accordance with a method ofclaim 81 in which at least one of R¹ and R² is H and in which R¹³² is anelectron donating group; and converting the compound of formula (CV) tothe cyclopentene.
 83. A method according to claim 82, wherein saidconverting is carried out in the presence of a Lewis acid.
 84. A methodfor preparing a dihydrofuran, said method comprising: providing acompound of formula (CV) in accordance with a method of claim 81 inwhich at least one of R¹ and R² is H, in which R¹³² is an electrondonating group, and in which R³ is a silyloxy group; and converting thecompound of formula (CV) to the dihydrofuran.
 85. A method according toclaim 84, wherein said converting is carried out in the presence of afluoride.
 86. A method for preparing a butenolide, said methodcomprising: providing a compound of formula (CV) in accordance with amethod of claim 81 in which at least one of R¹ and R² is H, in whichR¹³² is an electron donating group, in which Y is a carboxylic acidester of the formula —COOR¹⁶⁰ ₁, and in which R¹⁶⁰ is a tertiary alkylmoiety; and converting the compound of formula (CV) to the butenolide.87. A method according to claim 86, wherein said converting is carriedout in the presence of Lewis acid catalyst.
 88. A method of producing acompound having the following formula (CVII):

where each of R¹, R², R³, R¹³², R¹³³, and R¹³⁴ are defined as in claim81; and where Y′ is an alkyl group, an aldehyde group, a ketone, or avinyl group; said method comprising: providing a compound of formula(CV) in accordance with a method of claim 81; and converting thecompound of formula (CV) to the compound of formula (CVII).
 89. A methodaccording to claim 88, wherein R² is H; R¹ and R³, together with theatoms to which they are bonded, form a phenyl ring; R¹³² is H; R¹³³ is a4-alkoxyphenyl group; R¹³⁴ is a phenyl group; Y is a carboxylic acidester; and Y′ is an aldehyde group, a hydroxymethyl group, a vinylgroup, or an ethyl group.
 90. A method of producing a compound havingthe following formula (CVIII):

wherein each of R¹³², R¹³³, R¹³⁴, and Y are defined as in claim 81 andwhere R¹³⁵ is a carboxylic acid group, a carboxylic acid derivative, oran amino group, said method comprising: providing a compound of formula(CV) in accordance with a method of claim 81; and converting thecompound of formula (CV) to the compound of formula (CVIII).
 91. Amethod of producing a compound having the following formula (CIX):

where each of R¹³², R¹³³, R¹³⁴, and Y are defined as in claim 90; whereR¹³⁵ is a carboxylic acid group or a carboxylic acid derivative; andwhere R¹³⁶ represents an aryl group or an alkyl group; said methodcomprising: providing a compound of formula (CV) in accordance with amethod of claim 90 in which R¹³⁵ is a carboxylic acid group or acarboxylic acid derivative; and converting the compound of formula (CV)to the compound of formula (CIX).
 92. A method of producing a compoundhaving the following formula (CX):

where each of R¹³³, R¹³⁴, and R¹³⁶ are defined as in claim 88; whereR¹³⁷ is H and R¹³⁸ represents an amino group or R¹³⁷ and R¹³⁸, togetherwith the carbon atom to which they are bonded, represent a carbonylmoiety; where each R¹³⁹ independently represents an alkyl group, an arylgroup, a halogen, a hydroxy group, an amino group, a thiol group, analkyl thiol group, an aryl thiol group or two or more of R¹³⁹, togetherwith that atoms to which they are bonded, form a 5-12 membered ring; andwhere p represents an integer from 0 to 4; said method comprising:providing a compound having formula (CIX) in accordance with a method ofclaim 91 in which R¹³⁵ is a carboxylic acid group or a carboxylic acidderivative and in which R¹³² has the formula:

and converting the compound having formula (CIX) to the compound havingformula (CX).
 93. A method of catalyzing an aryldiazomethane or avinyldiazomethane cyclopropanation reaction, said method comprising:providing a aryldiazomethane or a vinyldiazomethane; providing adirhodium catalyst composition according to claim 1; and contacting thearyldiazomethane or the vinyldiazomethane with the dirhodium catalystcomposition under conditions effective to catalyze the aryldiazomethaneor vinyldiazomethane cyclopropanation reaction.
 94. A compound producedby a method according to claim
 93. 95. A compound containing a C—C bond,wherein said C—C bond is produced using a method according to claim 93.96. A method of producing optionally substituted cycloheptadienes oroptionally substituted bicyclooctadienes, said method comprising:providing a diazo compound having the formula:

where R¹, R², and R³ are independently selected from H, alkyl, aryl,silyloxy, or vinyl or where R¹ and R³, together with the atoms to whichthey are bonded, form a 5-12 membered ring; where Y is an electronwithdrawing group; and converting the diazo compound with a optionallysubstituted homocyclic, heterocyclic, or non-cyclic diene in thepresence of a dirhodium catalyst composition according to claim 1 underconditions effective to produce the compound.
 97. A method according toclaim 96, wherein the optionally substituted homocyclic, heterocyclic,or non-cyclic diene has the formula:

in which each of R¹⁴⁴, R¹⁴⁶, R¹⁴⁷, and R¹⁴⁸ independently represent analkyl group, an aryl group, an alkoxy group, a halogen, hydrogen, anacyl group, a hydroxy group, a thiol group, an alkyl thiol or aryl thiolgroup, a carboxylic acid group, a carboxylic acid derivative, or asilyloxy group or in which two or more of R¹⁴⁴, R¹⁴⁶, R¹⁴⁷, and R¹⁴⁸,together with the atom or atoms to which they are bonded, form a 5-12membered ring; and in which each of R¹⁴³ and R¹⁴⁵ independentlyrepresent an alkyl group, an aryl group, an alkoxy group, a halogen,hydrogen, an acyl group, a hydroxy group, a thiol group, an alkyl thiolor aryl thiol group, a carboxylic acid group, a carboxylic acidderivative, or a silyloxy group, or in which R¹⁴³ and R¹⁴⁵ togetherrepresent a —O— moiety, a —S— moiety, a substituted or unsubstitutedbivalent amino moiety, or a substituted or unsubstituted methylene orethylene moiety; and in which the optionally substitutedcycloheptadienes or optionally substituted bicyclooctadienes areoptionally substituted cyclohepta-1,5 dienes or optionally substituted8-aza-bicyclo[3.2.1]octa-2,6 dienes having the following formula (CXI):


98. A method according to claim 97, wherein R¹⁴³ and R¹⁴⁵ togetherrepresent a substituted or unsubstituted bivalent amino moiety havingthe formula —N(R¹⁵⁰)— in which R¹⁵⁰ is H, an aryl group, or alkyl group.99. A method for producing a 3-aryltropane, said method comprising:providing a compound of formula (CXI) in accordance with a method ofclaim 98; and converting the compound having formula (CXI) to a3-aryltropane using an aryl Grignard reagent.
 100. A method according toclaim 99, wherein the 3-aryltropane has the formula:

in which R¹⁵¹ is H, an aryl group, or an alkyl group; R¹⁵² is an arylgroup; R¹⁵³ represents H or a C1-C12 ketone; and R¹⁵⁴ represents H or aC1-C12 ketone.
 101. A method of catalyzing a [3+4] annulation reaction,said method comprising: providing a vinyldiazomethane; providing adirhodium catalyst composition according to claim 1; and contacting thevinyldiazomethane with the dirhodium catalyst composition underconditions effective to produce a seven or eight membered ring or ringsystem.
 102. A compound containing a seven or eight membered ring orring system produced by a method according to claim
 101. 103. A compoundcontaining a seven or eight membered ring or ring system, wherein saidseven or eight membered ring or ring system is produced using a methodaccording to claim
 101. 104. A method for producing a compound havingthe following formula (CXII):

wherein R¹, R², and R³ are independently selected from H, an alkylgroup, an aryl group, or a vinyl group or where R¹ and R³, together withthe atoms to which they are bonded, form a 5-12 membered ring; Y is anelectron withdrawing group; and R⁵⁴, R⁵⁵, R⁵⁶, R⁵⁷, R⁵⁸, and R⁵⁹ areindependently selected from the group consisting of H, alkyl, aryl,halogen, and alkoxy, said method comprising: providing a1,3-cyclohexadiene having the formula:

and converting the 1,3-cyclohexadiene with a diazo compound having theformula:

in the presence of a dirhodium catalyst composition according to claim 1and under conditions effective to produce the compound of formula(CXII).
 105. A method for making a compound having the following formula(CXIII):

wherein R¹, R², and R³ are independently selected from H, an alkylgroup, an aryl group, or a vinyl group or where R¹ and R³, together withthe atoms to which they are bonded, form a 5-12 membered ring; Y is anelectron withdrawing group; and R⁵⁴, R⁵⁵, R⁵⁶, R⁵⁸, and R⁵⁹ areindependently selected from the group consisting of H, alkyl, aryl,halogen, and alkoxy, said method comprising: providing a compound offormula (CXII) in accordance with a method of claim 104, wherein R⁵⁷ isH; and converting the compound of formula (CXII) under conditionseffective to form the compound of formula (CXIII).
 106. A methodaccording to claim 105, wherein R¹ and R³, together with the atoms towhich they are bonded, form an aromatic ring.
 107. A method forpreparing a compound having the following formula (CXIV):

wherein R¹, R², and R³ are independently selected from H, an alkylgroup, an aryl group, or a vinyl group or where R¹ and R³, together withthe atoms to which they are bonded, form a 5-12 membered ring; R⁵⁴, R⁵⁵,R⁵⁶, R⁵⁸, and R⁶⁵ are independently selected from the group consistingof H, alkyl groups, aryl groups, halogen, amino groups, alkoxy groups,hydroxy groups, and acid groups; R⁶² represents an alkyl moiety; or R⁶⁵and R⁶² together represent the atoms necessary to complete a 5-12membered ring, said method comprising: providing a compound of formula(CXIII) in accordance with a method of claim 105; and converting thecompound of formula (CXIII) under conditions effective to produce thecompound having formula (CXIV).
 108. for preparing a compound having thefollowing formula (CXIV):

where each of R¹, R², R³, R⁵⁴, R⁵⁵, R⁵⁶, and R⁵⁸ are defined as in claim93; and where R⁶⁰ is H and R⁶¹ represents a substituted or unsubstitutedamine or R⁶⁰ and R⁶¹, together with the carbon atom to which they arebonded, represent a carbonyl moiety, said method comprising: providing acompound of formula (CXII) in accordance with a method of claim 104,wherein Y is an electron withdrawing group and R⁵⁷ and R⁵⁹ are H; andconverting the compound of formula (CXII) under conditions effective toform the compound of formula (CXV).
 109. A method according to claim108, wherein R¹ and R³, together with the atoms to which they arebonded, form an aromatic ring.